11-67521123-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016366.3(CABP2):c.281G>A(p.Arg94Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,612,864 control chromosomes in the GnomAD database, including 247,091 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.43 ( 17502 hom., cov: 29)

Exomes 𝑓: 0.55 ( 229589 hom. )

Consequence

CABP2
NM_016366.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.114

Publications

48 publications found

Variant links:

Genes affected

CABP2 (HGNC:1385): (calcium binding protein 2) This gene belongs to a subfamily of calcium binding proteins that share similarity to calmodulin. Like calmodulin, these family members can likely stimulate calmodulin-dependent kinase II and the protein phosphatase calcineurin. Calcium binding proteins are an important component of calcium mediated cellular signal transduction. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

CABP2 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 93
Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CABP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.3817655E-6).

BP6

Variant 11-67521123-C-T is Benign according to our data. Variant chr11-67521123-C-T is described in ClinVar as Benign. ClinVar VariationId is 506033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABP2	NM_016366.3 link	c.281G>A	p.Arg94Gln	missense_variant	Exon 4 of 7	ENST00000294288.5	NP_057450.2	Q9NPB3-1
CABP2	NM_001318496.2 link	c.299G>A	p.Arg100Gln	missense_variant	Exon 4 of 7		NP_001305425.1	Q9NPB3F1T0K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABP2	ENST00000294288.5 link	c.281G>A	p.Arg94Gln	missense_variant	Exon 4 of 7	1	NM_016366.3	ENSP00000294288.4		Q9NPB3-1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65787

AN:

151606

Hom.:

17497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.572

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.679

Gnomad EAS

AF:

0.683

Gnomad SAS

AF:

0.642

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.482

GnomAD2 exomes

AF:

0.529

AC:

132663

AN:

250936

AF XY:

0.547

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.674

Gnomad EAS exome

AF:

0.696

Gnomad FIN exome

AF:

0.541

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.547

GnomAD4 exome

AF:

0.553

AC:

808562

AN:

1461140

Hom.:

229589

Cov.:

AF XY:

0.559

AC XY:

406332

AN XY:

726896

show subpopulations

African (AFR)

AF:

0.0938

AC:

3141

AN:

33480

American (AMR)

AF:

0.371

AC:

16580

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.677

AC:

17693

AN:

26134

East Asian (EAS)

AF:

0.676

AC:

26853

AN:

39698

South Asian (SAS)

AF:

0.635

AC:

54735

AN:

86244

European-Finnish (FIN)

AF:

0.541

AC:

28609

AN:

52880

Middle Eastern (MID)

AF:

0.565

AC:

3259

AN:

5768

European-Non Finnish (NFE)

AF:

0.562

AC:

624725

AN:

1111834

Other (OTH)

AF:

0.546

AC:

32967

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

18485

36971

55456

73942

92427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17324

34648

51972

69296

86620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.434

AC:

65789

AN:

151724

Hom.:

17502

Cov.:

AF XY:

0.441

AC XY:

32647

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.110

AC:

4537

AN:

41378

American (AMR)

AF:

0.439

AC:

6689

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.679

AC:

2352

AN:

3464

East Asian (EAS)

AF:

0.682

AC:

3501

AN:

5132

South Asian (SAS)

AF:

0.642

AC:

3078

AN:

4792

European-Finnish (FIN)

AF:

0.538

AC:

5670

AN:

10540

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.563

AC:

38245

AN:

67878

Other (OTH)

AF:

0.487

AC:

1024

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1572

3145

4717

6290

7862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.532

Hom.:

99716

Bravo

AF:

0.409

TwinsUK

AF:

0.563

AC:

2089

ALSPAC

AF:

0.569

AC:

2193

ESP6500AA

AF:

0.127

AC:

558

ESP6500EA

AF:

0.568

AC:

4879

ExAC

AF:

0.528

AC:

64121

Asia WGS

AF:

0.598

AC:

2075

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Arg94Gln in exon 4 of CABP2: This variant is not expected to have clinical sig nificance because it has been identified in 69.33% (5982/8628) of East Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs2276118). -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive nonsyndromic hearing loss 93

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

.;T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.87

D;D;D

MetaRNN

Benign

0.0000034

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.14

.;N;.

PhyloP100

0.11

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.63

N;N;.

REVEL

Benign

0.057

Sift

Benign

0.30

T;T;.

Sift4G

Benign

0.34

T;T;.

Polyphen

0.27

B;P;.

Vest4

0.051

MPC

0.36

ClinPred

0.010

GERP RS

3.6

Varity_R

0.069

gMVP

0.40

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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