rs2634553

Variant names:

• chr3-111331399-A-C
• rs2634553
• ENST00000460744.1:c.-325-33114A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000460744.1(CD96):​c.-325-33114A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,170 control chromosomes in the GnomAD database, including 2,671 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2671 hom., cov: 32)
• Consequence: CD96 ENST00000460744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD96	ENST00000460744.1	c.-325-33114A>C		intron_variant	Intron 1 of 4	4		ENSP00000475194.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22801 AN: 152052 Hom.: 2661 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0579

Gnomad OTH AF: 0.134

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.150 AC: 22836 AN: 152170 Hom.: 2671 Cov.: 32 AF XY: 0.156 AC XY: 11590 AN XY: 74380

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.0821

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.0579

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0726 Hom.: 1363

Bravo AF: 0.152

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2634553; hg19: chr3-111050246;