chr3-111578302-G-A

Variant names:

• chr3-111578302-G-A
• rs1513326
• NM_005816.5:c.544-725G>A

Variant summary

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

The NM_005816.5(CD96):​c.544-725G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,246 control chromosomes in the GnomAD database, including 248 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 0.050 (248 hom., cov: 33)
• Consequence: CD96 NM_005816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 0 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD96	NM_005816.5	c.544-725G>A		intron_variant	Intron 3 of 13	ENST00000352690.9	NP_005807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD96	ENST00000352690.9	c.544-725G>A		intron_variant	Intron 3 of 13	1	NM_005816.5	ENSP00000342040.3

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7606 AN: 152128 Hom.: 248 Cov.: 33

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0433

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0499 AC: 7602 AN: 152246 Hom.: 248 Cov.: 33 AF XY: 0.0481 AC XY: 3582 AN XY: 74448

African (AFR) AF: 0.0137 AC: 568 AN: 41550

American (AMR) AF: 0.0621 AC: 950 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4822

European-Finnish (FIN) AF: 0.0433 AC: 459 AN: 10602

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0742 AC: 5044 AN: 68002

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0604 Hom.: 100

Bravo AF: 0.0507

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.47
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1513326; hg19: chr3-111297149;