3-111333212-A-G

Variant names:

• chr3-111333212-A-G
• rs2971366
• ENST00000460744.1:c.-325-31301A>G

Variant summary

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

The ENST00000460744.1(CD96):​c.-325-31301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,954 control chromosomes in the GnomAD database, including 5,185 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 (5185 hom., cov: 32)
• Consequence: CD96 ENST00000460744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 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.-325-31301A>G		intron_variant	Intron 1 of 4	4		ENSP00000475194.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32939 AN: 151840 Hom.: 5172 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.217 AC: 32986 AN: 151954 Hom.: 5185 Cov.: 32 AF XY: 0.221 AC XY: 16430 AN XY: 74242

African (AFR) AF: 0.432 AC: 17901 AN: 41410

American (AMR) AF: 0.132 AC: 2012 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3470

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

South Asian (SAS) AF: 0.225 AC: 1084 AN: 4814

European-Finnish (FIN) AF: 0.205 AC: 2158 AN: 10518

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7150 AN: 67986

Other (OTH) AF: 0.194 AC: 409 AN: 2112

Alfa AF: 0.145 Hom.: 8185

Bravo AF: 0.224

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs2971366; hg19: chr3-111052059;