rs7643682

Variant names:

• chr3-111547729-C-T
• rs7643682
• NM_005816.5:c.418+2327C>T

Variant summary

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

The NM_005816.5(CD96):​c.418+2327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 152,134 control chromosomes in the GnomAD database, including 1,444 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 0.081 (1444 hom., cov: 32)
• Consequence: CD96 NM_005816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005816.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD96	NM_005816.5	MANE Select	c.418+2327C>T		intron	N/A	NP_005807.1
	CD96	NM_198196.3		c.418+2327C>T		intron	N/A	NP_937839.1
	CD96	NM_001410800.1		c.418+2327C>T		intron	N/A	NP_001397729.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD96	ENST00000352690.9	TSL:1 MANE Select	c.418+2327C>T		intron	N/A	ENSP00000342040.3
	CD96	ENST00000283285.10	TSL:1	c.418+2327C>T		intron	N/A	ENSP00000283285.5
	CD96	ENST00000438817.6	TSL:1	c.418+2327C>T		intron	N/A	ENSP00000389801.2

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12355 AN: 152016 Hom.: 1440 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.00632

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0814 AC: 12386 AN: 152134 Hom.: 1444 Cov.: 32 AF XY: 0.0788 AC XY: 5864 AN XY: 74374

African (AFR) AF: 0.260 AC: 10791 AN: 41462

American (AMR) AF: 0.0316 AC: 483 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3468

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5176

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4818

European-Finnish (FIN) AF: 0.00632 AC: 67 AN: 10594

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 695 AN: 68008

Other (OTH) AF: 0.0638 AC: 135 AN: 2116

Alfa AF: 0.0518 Hom.: 108

Bravo AF: 0.0914

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-0.60
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: rs7643682; hg19: chr3-111266576;