3-111333764-T-C

Variant summary

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

The ENST00000460744.1(CD96):c.-325-30749T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,118 control chromosomes in the GnomAD database, including 6,691 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 0.27 (6691 hom., cov: 32)
• Consequence: CD96 ENST00000460744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722

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 = 0.444 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.-325-30749T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41212 AN: 152000 Hom.: 6679 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.271 AC: 41253 AN: 152118 Hom.: 6691 Cov.: 32 AF XY: 0.276 AC XY: 20522 AN XY: 74366

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.262

Alfa AF: 0.203 Hom.: 1691

Bravo AF: 0.275

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.80
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1489032; hg19: chr3-111052611;