chr3-111331399-A-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• C syndrome

  Inheritance: Unknown, AD, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000460744.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD96	ENST00000460744.1	TSL:4	c.-325-33114A>C		intron	N/A	ENSP00000475194.1	U3KPT0

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

African (AFR) AF: 0.304 AC: 12631 AN: 41496

American (AMR) AF: 0.0821 AC: 1256 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 140 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1780 AN: 5154

South Asian (SAS) AF: 0.203 AC: 981 AN: 4824

European-Finnish (FIN) AF: 0.169 AC: 1790 AN: 10588

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0579 AC: 3940 AN: 68026

Other (OTH) AF: 0.137 AC: 289 AN: 2106

Alfa AF: 0.0852 Hom.: 4340

Bravo AF: 0.152

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.58
PhyloP100		-0.77

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2634553;

hg19: chr3-111050246;