rs1881681

Variant names:

• chr3-111447727-C-A
• rs1881681
• ENST00000460744.1:c.-99+81809C>A

Variant summary

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

The ENST00000460744.1(CD96):​c.-99+81809C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,002 control chromosomes in the GnomAD database, including 6,898 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 0.23 (6898 hom., cov: 32)
• Consequence: CD96 ENST00000460744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582
• Publications: 2 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

LOC105374039 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374039	XR_001740846.1	n.223+81809C>A		intron_variant	Intron 2 of 2
LOC105374039	XR_007096275.1	n.224-30525C>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD96	ENST00000460744.1	c.-99+81809C>A		intron_variant	Intron 3 of 4	4		ENSP00000475194.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35384 AN: 151884 Hom.: 6869 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.233 AC: 35462 AN: 152002 Hom.: 6898 Cov.: 32 AF XY: 0.230 AC XY: 17078 AN XY: 74276

African (AFR) AF: 0.538 AC: 22284 AN: 41404

American (AMR) AF: 0.126 AC: 1932 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3472

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5180

South Asian (SAS) AF: 0.0813 AC: 392 AN: 4820

European-Finnish (FIN) AF: 0.157 AC: 1655 AN: 10536

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8144 AN: 67994

Other (OTH) AF: 0.204 AC: 432 AN: 2114

Alfa AF: 0.158 Hom.: 2627

Bravo AF: 0.245

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.31
PhyloP100		-0.58

Splicing

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

Other links and lift over

dbSNP: rs1881681; hg19: chr3-111166574;