rs35211634

Positions:

chr11-59845386-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005142.3(CBLIF):c.68A>G(p.Gln23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0582 in 1,611,514 control chromosomes in the GnomAD database, including 3,993 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 1103 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2890 hom. )

Consequence

CBLIF
NM_005142.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -2.89

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:

CBLIF (HGNC:):

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=0.009813279).

BP6

Variant 11-59845386-T-C is Benign according to our data. Variant chr11-59845386-T-C is described in ClinVar as [Benign]. Clinvar id is 1742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-59845386-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBLIF	NM_005142.3 linkuse as main transcript	c.68A>G	p.Gln23Arg	missense_variant	1/9	ENST00000257248.3	NP_005133.2	P27352-1
CBLIF	XM_011544939.4 linkuse as main transcript	c.68A>G	p.Gln23Arg	missense_variant	1/9		XP_011543241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CBLIF	ENST00000257248.3 linkuse as main transcript	c.68A>G	p.Gln23Arg	missense_variant	1/9	1	NM_005142.3	ENSP00000257248.2	P27352-1
CBLIF	ENST00000525058.5 linkuse as main transcript	n.68A>G		non_coding_transcript_exon_variant	1/9	2		ENSP00000433196.1	E9PM21
CBLIF	ENST00000532070.1 linkuse as main transcript	n.114A>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0950

AC:

14442

AN:

151996

Hom.:

1094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.0428

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.0363

Gnomad SAS

AF:

0.0356

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0501

Gnomad OTH

AF:

0.0708

GnomAD3 exomes

AF:

0.0589

AC:

14807

AN:

251222

Hom.:

727

AF XY:

0.0550

AC XY:

7468

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.0261

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.0396

Gnomad SAS exome

AF:

0.0372

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.0507

Gnomad OTH exome

AF:

0.0441

GnomAD4 exome

AF:

0.0544

AC:

79327

AN:

1459400

Hom.:

2890

Cov.:

AF XY:

0.0532

AC XY:

38661

AN XY:

726190

show subpopulations

Gnomad4 AFR exome

AF:

0.216

Gnomad4 AMR exome

AF:

0.0266

Gnomad4 ASJ exome

AF:

0.0175

Gnomad4 EAS exome

AF:

0.0290

Gnomad4 SAS exome

AF:

0.0369

Gnomad4 FIN exome

AF:

0.105

Gnomad4 NFE exome

AF:

0.0514

Gnomad4 OTH exome

AF:

0.0552

GnomAD4 genome

AF:

0.0953

AC:

14494

AN:

152114

Hom.:

1103

Cov.:

AF XY:

0.0958

AC XY:

7129

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.0426

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.0362

Gnomad4 SAS

AF:

0.0356

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0500

Gnomad4 OTH

AF:

0.0705

Alfa

AF:

0.0542

Hom.:

752

Bravo

AF:

0.0962

TwinsUK

AF:

0.0453

AC:

168

ALSPAC

AF:

0.0509

AC:

196

ESP6500AA

AF:

0.197

AC:

866

ESP6500EA

AF:

0.0481

AC:

413

ExAC

AF:

0.0607

AC:

7370

Asia WGS

AF:

0.0640

AC:

222

AN:

3478

EpiCase

AF:

0.0431

EpiControl

AF:

0.0433

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

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 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Intrinsic factor deficiency, congenital, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 15, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0020

DANN

Benign

0.20

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.37

REVEL

Benign

0.20

Sift

Benign

1.0

Sift4G

Benign

0.84

Vest4

0.018

MPC

0.13

ClinPred

0.0061

GERP RS

-4.4

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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