rs1788114

Positions:

• chr18-69896736-T-C

Variant summary

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

The NM_001303618.2(CD226):​c.383-691A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,996 control chromosomes in the GnomAD database, including 18,611 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 0.48 (18611 hom., cov: 31)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

Genes affected

CD226 (HGNC:16961): (CD226 molecule) This gene encodes a glycoprotein expressed on the surface of NK cells, platelets, monocytes and a subset of T cells. It is a member of the Ig-superfamily containing 2 Ig-like domains of the V-set. The protein mediates cellular adhesion of platelets and megakaryocytic cells to vascular endothelial cells. The protein also plays a role in megakaryocytic cell maturation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

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 = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD226	NM_001303618.2	c.383-691A>G		intron_variant		ENST00000582621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000582621.6	c.383-691A>G		intron_variant		1	NM_001303618.2	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72483 AN: 151878 Hom.: 18562 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.478 AC: 72607 AN: 151996 Hom.: 18611 Cov.: 31 AF XY: 0.468 AC XY: 34803 AN XY: 74288

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.505

Alfa AF: 0.452 Hom.: 4415

Bravo AF: 0.498

Asia WGS AF: 0.356 AC: 1241 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	0.28
DANN	Benign	0.68

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: rs1788114; hg19: chr18-67563972;