rs11661553

chr18-69877401-T-A

Variant summary

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

The NM_001303618.2(CD226):c.728-4155A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,100 control chromosomes in the GnomAD database, including 10,804 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 0.34 (10804 hom., cov: 31)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD226	NM_001303618.2	c.728-4155A>T		intron_variant		ENST00000582621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000582621.6	c.728-4155A>T		intron_variant		1	NM_001303618.2	P1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51970 AN: 151982 Hom.: 10812 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.342 AC: 51950 AN: 152100 Hom.: 10804 Cov.: 31 AF XY: 0.350 AC XY: 26013 AN XY: 74338

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.338

Alfa AF: 0.381 Hom.: 1531

Bravo AF: 0.321

Asia WGS AF: 0.462 AC: 1605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.45
Dann	Benign	0.31

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: rs11661553; hg19: chr18-67544637;