18-69958049-C-T

Position:

• chr18-69958049-C-T

Variant summary

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

The ENST00000579496.5(CD226):​c.-127+3543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,008 control chromosomes in the GnomAD database, including 18,736 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 0.45 (18736 hom., cov: 31)
• Consequence: CD226 ENST00000579496.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	XM_006722374.4	c.13+3543G>A		intron_variant			XP_006722437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000579496.5	c.-127+3543G>A		intron_variant		5		ENSP00000463927.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68134 AN: 151890 Hom.: 18723 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.448 AC: 68157 AN: 152008 Hom.: 18736 Cov.: 31 AF XY: 0.456 AC XY: 33850 AN XY: 74298

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.449

Alfa AF: 0.549 Hom.: 30652

Bravo AF: 0.425

Asia WGS AF: 0.562 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.33
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1539964; hg19: chr18-67625285;