rs2634553

Positions:

• chr3-111331399-A-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]

(HGNC:):

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/exons	MANE	Protein	UniProt
		n.111331399A>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD96	ENST00000460744.1	c.-325-33114A>C		intron_variant		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;