NM_005142.3(CBLIF):c.1211C>G (p.Pro404Arg) AND Hereditary intrinsic factor deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 26, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001369189.4

Allele description [Variation Report for NM_005142.3(CBLIF):c.1211C>G (p.Pro404Arg)]

NM_005142.3(CBLIF):c.1211C>G (p.Pro404Arg)

Gene:

CBLIF:cobalamin binding intrinsic factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q12.1

Genomic location:

Preferred name:

NM_005142.3(CBLIF):c.1211C>G (p.Pro404Arg)

HGVS:

NC_000011.10:g.59829527G>C
NG_008120.1:g.20975C>G
NM_005142.3:c.1211C>GMANE SELECT
NP_005133.2:p.Pro404Arg
NC_000011.9:g.59597000G>C

Protein change:

P404R

Links:

dbSNP: rs1460997213

NCBI 1000 Genomes Browser:

rs1460997213

Molecular consequence:

NM_005142.3:c.1211C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary intrinsic factor deficiency (IFD)
Synonyms:: PERNICIOUS ANEMIA, CONGENITAL, DUE TO DEFECT OF INTRINSIC FACTOR; Intrinsic factor deficiency; Congenital intrinsic factor deficiency
Identifiers:: MONDO: MONDO:0009852; MedGen: C1394891; Orphanet: 332; OMIM: 261000

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001565619	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 26, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001565619

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 26, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001565619.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GIF-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 404 of the GIF protein (p.Pro404Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine