NM_001303618.2:c.728-8145C>T

Variant names:

• chr18-69881391-G-A
• rs1124980
• NM_001303618.2:c.728-8145C>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.728-8145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,942 control chromosomes in the GnomAD database, including 26,683 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 0.58 (26683 hom., cov: 31)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD226	NM_001303618.2	c.728-8145C>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.728-8145C>T		intron_variant	Intron 3 of 5	1	NM_001303618.2	ENSP00000461947.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88765 AN: 151824 Hom.: 26656 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.585 AC: 88836 AN: 151942 Hom.: 26683 Cov.: 31 AF XY: 0.592 AC XY: 43923 AN XY: 74224

African (AFR) AF: 0.462 AC: 19122 AN: 41426

American (AMR) AF: 0.696 AC: 10632 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4462 AN: 5150

South Asian (SAS) AF: 0.647 AC: 3113 AN: 4810

European-Finnish (FIN) AF: 0.640 AC: 6732 AN: 10524

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41139 AN: 67978

Other (OTH) AF: 0.568 AC: 1197 AN: 2106

Alfa AF: 0.593 Hom.: 44988

Bravo AF: 0.583

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.19
PhyloP100		0.011
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: rs1124980; hg19: chr18-67548627;