NM_001303618.2:c.728-4155A>T

Variant names:

• chr18-69877401-T-A
• rs11661553
• NM_001303618.2:c.728-4155A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CD226	NM_001303618.2	c.728-4155A>T		intron_variant	Intron 3 of 5	ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.728-4155A>T		intron_variant	Intron 3 of 5	1	NM_001303618.2	ENSP00000461947.1

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

African (AFR) AF: 0.100 AC: 4164 AN: 41520

American (AMR) AF: 0.405 AC: 6192 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1105 AN: 3470

East Asian (EAS) AF: 0.601 AC: 3097 AN: 5154

South Asian (SAS) AF: 0.407 AC: 1960 AN: 4812

European-Finnish (FIN) AF: 0.516 AC: 5451 AN: 10570

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28831 AN: 67968

Other (OTH) AF: 0.338 AC: 713 AN: 2112

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
PhyloP100		-0.031
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11661553; hg19: chr18-67544637;