chr3-111567528-G-C

Position:

• chr3-111567528-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.493

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 (HGNC:):

ACMG classification

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	Protein	UniProt
CD96	NM_005816.5	c.424G>C	p.Ala142Pro	missense_variant	3/14	ENST00000352690.9	NP_005807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD96	ENST00000352690.9	c.424G>C	p.Ala142Pro	missense_variant	3/14	1	NM_005816.5	ENSP00000342040.3

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4663 AN: 152146 Hom.: 178 Cov.: 33

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

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.: 27 AF XY: 0.0139 AC XY: 10076 AN XY: 723742

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.: 33 AF XY: 0.0311 AC XY: 2316 AN XY: 74440

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.: 45

Bravo AF: 0.0382

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00623 AC: 24

ESP6500AA AF: 0.0508 AC: 224

ESP6500EA AF: 0.00581 AC: 50

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CD96-related disorder Benign:1

Benign, no assertion criteria provided

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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.7
DANN	Benign	0.60
DEOGEN2	Benign	0.029	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.00064	N
LIST_S2	Benign	0.30	T;T;T
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N;N;.
PrimateAI	Benign	0.27	T
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	T
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

Other links and lift over

dbSNP: rs2276872; hg19: chr3-111286375; COSMIC: COSV51916606; COSMIC: COSV51916606;