rs1009847

Positions:

• chr18-69883916-G-C

Variant summary

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

The NM_001303618.2(CD226):​c.728-10670C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,222 control chromosomes in the GnomAD database, including 3,792 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 0.20 (3792 hom., cov: 33)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471

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 (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD226	NM_001303618.2	c.728-10670C>G		intron_variant		ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.728-10670C>G		intron_variant		1	NM_001303618.2	ENSP00000461947	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30932 AN: 152104 Hom.: 3792 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.203 AC: 30942 AN: 152222 Hom.: 3792 Cov.: 33 AF XY: 0.196 AC XY: 14622 AN XY: 74430

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.00560

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.252

Alfa AF: 0.229 Hom.: 525

Bravo AF: 0.200

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.40

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: rs1009847; hg19: chr18-67551152;