rs57743896

Positions:

• chr18-69947298-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001303618.2(CD226):​c.46+63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0088 in 1,107,846 control chromosomes in the GnomAD database, including 75 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 0.0072 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0091 (71 hom.)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

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).
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00905 (8652/955712) while in subpopulation MID AF= 0.0246 (96/3902). AF 95% confidence interval is 0.0206. There are 71 homozygotes in gnomad4_exome. There are 4433 alleles in male gnomad4_exome subpopulation. Median coverage is 12. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	NM_001303618.2	c.46+63G>A		intron_variant		ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.46+63G>A		intron_variant		1	NM_001303618.2	ENSP00000461947.1

Frequencies

GnomAD3 genomes AF: 0.00720 AC: 1095 AN: 152016 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00609

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00852

Gnomad FIN AF: 0.00444

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00934

Gnomad OTH AF: 0.00957

GnomAD4 exome AF: 0.00905 AC: 8652 AN: 955712 Hom.: 71 Cov.: 12 AF XY: 0.00900 AC XY: 4433 AN XY: 492630

Gnomad4 AFR exome AF: 0.00703

Gnomad4 AMR exome AF: 0.00398

Gnomad4 ASJ exome AF: 0.00605

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00960

Gnomad4 FIN exome AF: 0.00681

Gnomad4 NFE exome AF: 0.00993

Gnomad4 OTH exome AF: 0.00925

GnomAD4 genome AF: 0.00718 AC: 1093 AN: 152134 Hom.: 4 Cov.: 32 AF XY: 0.00715 AC XY: 532 AN XY: 74380

Gnomad4 AFR AF: 0.00607

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00811

Gnomad4 FIN AF: 0.00444

Gnomad4 NFE AF: 0.00934

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00762 Hom.: 1

Bravo AF: 0.00735

Asia WGS AF: 0.00722 AC: 27 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	2.5
DANN	Benign	0.35

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: rs57743896; hg19: chr18-67614534;