rs1788101

chr18-69873132-T-G

Variant summary

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

The NM_001303618.2(CD226):c.830+12A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,361,574 control chromosomes in the GnomAD database, including 12,053 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 0.17 (2987 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9066 hom.)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908

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 = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD226	NM_001303618.2	c.830+12A>C		intron_variant		ENST00000582621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000582621.6	c.830+12A>C		intron_variant		1	NM_001303618.2	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25436 AN: 152018 Hom.: 2981 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.0957

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.165

GnomAD3 exomes AF: 0.110 AC: 27492 AN: 249872 Hom.: 2125 AF XY: 0.106 AC XY: 14390 AN XY: 135118

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.0641

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.00272

Gnomad SAS exome AF: 0.0739

Gnomad FIN exome AF: 0.0865

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.113 AC: 136297 AN: 1209438 Hom.: 9066 Cov.: 17 AF XY: 0.112 AC XY: 68553 AN XY: 614634

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.0669

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.000962

Gnomad4 SAS exome AF: 0.0779

Gnomad4 FIN exome AF: 0.0886

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.168 AC: 25486 AN: 152136 Hom.: 2987 Cov.: 32 AF XY: 0.161 AC XY: 12007 AN XY: 74380

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0773

Gnomad4 FIN AF: 0.0817

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.168

Alfa AF: 0.124 Hom.: 2075

Bravo AF: 0.177

Asia WGS AF: 0.0760 AC: 266 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	0.041
Dann	Benign	0.59

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: rs1788101; hg19: chr18-67540368; COSMIC: COSV54611724; COSMIC: COSV54611724;