Variant 3-111567528-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005816.5(CD96):c.424G>C(p.Ala142Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,605,728 control chromosomes in the GnomAD database, including 1,218 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.031 ( 176 hom., cov: 33)

Exomes 𝑓: 0.015 ( 1042 hom. )

Consequence

CD96
NM_005816.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.493

Variant links:

Genes affected

CD96 (HGNC:16892): (CD96 molecule) The protein encoded by this gene belongs to the immunoglobulin superfamily. It is a type I membrane protein. The protein may play a role in the adhesive interactions of activated T and NK cells during the late phase of the immune response. It may also function in antigen presentation. Alternative splicing generates multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

CD96 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=0.0016770959).

BP6

Variant 3-111567528-G-C is Benign according to our data. Variant chr3-111567528-G-C is described in ClinVar as [Benign]. Clinvar id is 1538658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD96	NM_005816.5 linkuse as main transcript	c.424G>C	p.Ala142Pro	missense_variant	3/14	ENST00000352690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD96	ENST00000352690.9 linkuse as main transcript	c.424G>C	p.Ala142Pro	missense_variant	3/14	1	NM_005816.5	P2	P40200-2

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4663

AN:

152146

Hom.:

178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0571

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0651

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.0271

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00481

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0378

AC:

9495

AN:

251094

Hom.:

605

AF XY:

0.0319

AC XY:

4326

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.0547

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.0159

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00395

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0147

AC:

21372

AN:

1453464

Hom.:

1042

Cov.:

AF XY:

0.0139

AC XY:

10076

AN XY:

723742

show subpopulations

Gnomad4 AFR exome

AF:

0.0519

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.00315

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.0156

Gnomad4 FIN exome

AF:

0.000319

Gnomad4 NFE exome

AF:

0.00481

Gnomad4 OTH exome

AF:

0.0197

GnomAD4 genome

AF:

0.0306

AC:

4666

AN:

152264

Hom.:

176

Cov.:

AF XY:

0.0311

AC XY:

2316

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0570

Gnomad4 AMR

AF:

0.0652

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.150

Gnomad4 SAS

AF:

0.0271

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00481

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.0382

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.0508

AC:

224

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.0341

AC:

4141

Asia WGS

AF:

0.0810

AC:

280

AN:

3478

EpiCase

AF:

0.00409

EpiControl

AF:

0.00427

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CD96-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 14, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.62

Cadd

Benign

8.7

Dann

Benign

0.60

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.00064

LIST_S2

Benign

0.30

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

N;N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.49

N;N;N

REVEL

Benign

0.095

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.074

MPC

0.020

ClinPred

0.0038

GERP RS

4.4

Varity_R

0.046

gMVP

0.65

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