3-111333764-T-C

Variant names:

• chr3-111333764-T-C
• rs1489032
• ENST00000460744.1:c.-325-30749T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000460744.1(CD96):​c.-325-30749T>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
• 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, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD96	ENST00000460744.1	c.-325-30749T>C		intron_variant	Intron 1 of 4	4		ENSP00000475194.1

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

African (AFR) AF: 0.449 AC: 18623 AN: 41482

American (AMR) AF: 0.187 AC: 2858 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3472

East Asian (EAS) AF: 0.349 AC: 1804 AN: 5176

South Asian (SAS) AF: 0.285 AC: 1375 AN: 4824

European-Finnish (FIN) AF: 0.270 AC: 2857 AN: 10584

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12374 AN: 67982

Other (OTH) AF: 0.262 AC: 552 AN: 2110

Alfa AF: 0.202 Hom.: 1843

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
PhyloP100		-0.72

Splicing

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

Other links and lift over

dbSNP: rs1489032; hg19: chr3-111052611;