chr11-59835891-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005142.3(CBLIF):c.990C>T(p.Asn330Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00687 in 1,614,002 control chromosomes in the GnomAD database, including 548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 51 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 497 hom. )

Consequence

CBLIF
NM_005142.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.848

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

hereditary intrinsic factor deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

CBLIF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-59835891-G-A is Benign according to our data. Variant chr11-59835891-G-A is described in ClinVar as [Benign]. Clinvar id is 305031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.848 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBLIF	NM_005142.3 link	c.990C>T	p.Asn330Asn	synonymous_variant	Exon 7 of 9	ENST00000257248.3	NP_005133.2	P27352-1
CBLIF	XM_011544939.4 link	c.948C>T	p.Asn316Asn	synonymous_variant	Exon 7 of 9		XP_011543241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBLIF	ENST00000257248.3 link	c.990C>T	p.Asn330Asn	synonymous_variant	Exon 7 of 9	1	NM_005142.3	ENSP00000257248.2		P27352-1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1560

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0675

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.0594

Gnomad SAS

AF:

0.00748

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0216

AC:

5432

AN:

251384

AF XY:

0.0166

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.0552

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000528

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.00652

AC:

9528

AN:

1461742

Hom.:

497

Cov.:

AF XY:

0.00577

AC XY:

4197

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.00122

AC:

AN:

33478

American (AMR)

AF:

0.113

AC:

5039

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00371

AC:

AN:

26134

East Asian (EAS)

AF:

0.0737

AC:

2925

AN:

39700

South Asian (SAS)

AF:

0.00384

AC:

331

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000588

AC:

654

AN:

1111868

Other (OTH)

AF:

0.00722

AC:

436

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

717

1434

2151

2868

3585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0102

AC:

1557

AN:

152260

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

839

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

41554

American (AMR)

AF:

0.0674

AC:

1031

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.0593

AC:

307

AN:

5174

South Asian (SAS)

AF:

0.00727

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68032

Other (OTH)

AF:

0.0137

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00794

Hom.:

Bravo

AF:

0.0158

Asia WGS

AF:

0.0470

AC:

163

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary intrinsic factor deficiency

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.41

(source)

DANN

Benign

0.47

PhyloP100

-0.85

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr11-59835891-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over