11-67521123-C-T

Position:

chr11-67521123-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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:4

Conservation

PhyloP100: 0.114

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 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=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 id is 506033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-67521123-C-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
CABP2	NM_016366.3 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	4/7	ENST00000294288.5
CABP2	NM_001318496.2 linkuse as main transcript	c.299G>A	p.Arg100Gln	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CABP2	ENST00000294288.5 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	4/7	1	NM_016366.3		Q9NPB3-1
CABP2	ENST00000545205.2 linkuse as main transcript	c.*66G>A		3_prime_UTR_variant, NMD_transcript_variant	4/7	1
CABP2	ENST00000636477.1 linkuse as main transcript	c.233G>A	p.Arg78Gln	missense_variant	3/6	5
CABP2	ENST00000353903.9 linkuse as main transcript	c.110G>A	p.Arg37Gln	missense_variant	3/6	5		P1	Q9NPB3-2

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

GnomAD3 exomes

AF:

0.529

AC:

132663

AN:

250936

Hom.:

37877

AF XY:

0.547

AC XY:

74209

AN XY:

135656

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 SAS exome

AF:

0.635

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

Gnomad4 AFR exome

AF:

0.0938

Gnomad4 AMR exome

AF:

0.371

Gnomad4 ASJ exome

AF:

0.677

Gnomad4 EAS exome

AF:

0.676

Gnomad4 SAS exome

AF:

0.635

Gnomad4 FIN exome

AF:

0.541

Gnomad4 NFE exome

AF:

0.562

Gnomad4 OTH exome

AF:

0.546

GnomAD4 genome

AF:

0.434

AC:

65789

AN:

151724

Hom.:

17502

Cov.:

AF XY:

0.441

AC XY:

32647

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.679

Gnomad4 EAS

AF:

0.682

Gnomad4 SAS

AF:

0.642

Gnomad4 FIN

AF:

0.538

Gnomad4 NFE

AF:

0.563

Gnomad4 OTH

AF:

0.487

Alfa

AF:

0.557

Hom.:

57920

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	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:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Autosomal recessive nonsyndromic hearing loss 93

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

DANN

Uncertain

0.98

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

MutationTaster

Benign

0.11

P;P

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

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