3-111312576-G-C

Variant summary

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

The ENST00000460744.1(CD96):c.-326+19691G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,008 control chromosomes in the GnomAD database, including 4,469 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 0.22 (4469 hom., cov: 32)
• Consequence: CD96 ENST00000460744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD96	ENST00000460744.1	c.-326+19691G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32860 AN: 151890 Hom.: 4459 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.216 AC: 32909 AN: 152008 Hom.: 4469 Cov.: 32 AF XY: 0.213 AC XY: 15831 AN XY: 74296

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.0998

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.176

Alfa AF: 0.0907 Hom.: 139

Bravo AF: 0.230

Asia WGS AF: 0.148 AC: 513 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.86
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2056773; hg19: chr3-111031423;