3-111611214-G-T

Position:

• chr3-111611214-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005816.5(CD96):​c.1180+4422G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,978 control chromosomes in the GnomAD database, including 5,878 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 0.26 (5878 hom., cov: 32)
• Consequence: CD96 NM_005816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD96	NM_005816.5	c.1180+4422G>T		intron_variant		ENST00000352690.9	NP_005807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD96	ENST00000352690.9	c.1180+4422G>T		intron_variant		1	NM_005816.5	ENSP00000342040	P2
CD96	ENST00000283285.10	c.1228+4422G>T		intron_variant		1		ENSP00000283285	A2
CD96	ENST00000494798.1	c.1180+4422G>T		intron_variant, NMD_transcript_variant		2		ENSP00000417152

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38855 AN: 151860 Hom.: 5862 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.256 AC: 38912 AN: 151978 Hom.: 5878 Cov.: 32 AF XY: 0.257 AC XY: 19107 AN XY: 74282

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.217

Alfa AF: 0.212 Hom.: 1333

Bravo AF: 0.261

Asia WGS AF: 0.229 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.9
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs16858329; hg19: chr3-111330061;