rs893001

chr18-69849610-A-Cchr18-69849610-A-G

Variant summary

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

The ENST00000578928.1(CD226):c.110-7215T>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 30,288 control chromosomes in the GnomAD database, including 195 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 (195 hom., cov: 0)
• Consequence: CD226 ENST00000578928.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000578928.1	c.110-7215T>G		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.173 AC: 5242 AN: 30252 Hom.: 195 Cov.: 0

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0935

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0900

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.174 AC: 5259 AN: 30288 Hom.: 195 Cov.: 0 AF XY: 0.173 AC XY: 2527 AN XY: 14612

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.0935

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0900

Gnomad4 OTH AF: 0.149

Alfa AF: 0.446 Hom.: 1958

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.82
Dann	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs893001; hg19: chr18-67516846; COSMIC: COSV66930141;