chr11-59831732-C-T

Position:

chr11-59831732-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005142.3(CBLIF):c.1138G>A(p.Val380Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,608,588 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 2 hom. )

Consequence

CBLIF
NM_005142.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.639

Variant links:

Genes affected

CBLIF (HGNC:4268): (cobalamin binding intrinsic factor) This gene is a member of the cobalamin transport protein family. It encodes a glycoprotein secreted by parietal cells of the gastric mucosa and is required for adequate absorption of vitamin B12. Vitamin B12 is necessary for erythrocyte maturation and mutations in this gene may lead to congenital pernicious anemia. [provided by RefSeq, Jul 2008]

CBLIF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005246401).

BP6

Variant 11-59831732-C-T is Benign according to our data. Variant chr11-59831732-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 788331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000834 (127/152192) while in subpopulation AMR AF= 0.00556 (85/15278). AF 95% confidence interval is 0.00461. There are 1 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLIF	NM_005142.3 linkuse as main transcript	c.1138G>A	p.Val380Ile	missense_variant	8/9	ENST00000257248.3	NP_005133.2
CBLIF	XM_011544939.4 linkuse as main transcript	c.1096G>A	p.Val366Ile	missense_variant	8/9		XP_011543241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBLIF	ENST00000257248.3 linkuse as main transcript	c.1138G>A	p.Val380Ile	missense_variant	8/9	1	NM_005142.3	ENSP00000257248	P1	P27352-1
CBLIF	ENST00000533067.1 linkuse as main transcript	n.185G>A		non_coding_transcript_exon_variant	2/2	3
CBLIF	ENST00000525058.5 linkuse as main transcript	c.*1105G>A		3_prime_UTR_variant, NMD_transcript_variant	8/9	2		ENSP00000433196

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000955

AC:

240

AN:

251420

Hom.:

AF XY:

0.000832

AC XY:

113

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00460

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000484

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.000447

AC:

651

AN:

1456396

Hom.:

Cov.:

AF XY:

0.000422

AC XY:

306

AN XY:

724952

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.00501

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000332

Gnomad4 OTH exome

AF:

0.000714

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152192

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00556

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000535

Hom.:

Bravo

AF:

0.00105

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000667

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary intrinsic factor deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.84

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.41

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.19

REVEL

Benign

0.025

Sift

Benign

0.40

Sift4G

Benign

0.27

Vest4

0.19

MVP

0.12

MPC

0.099

ClinPred

0.016

GERP RS

1.5

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over