rs1124980

Positions:

• chr18-69881391-G-A
• chr18-69881391-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• 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/exons	MANE	UniProt
CD226	NM_001303618.2	c.728-8145C>T		intron_variant		ENST00000582621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000582621.6	c.728-8145C>T		intron_variant		1	NM_001303618.2	P1

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

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.568

Alfa AF: 0.595 Hom.: 36147

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

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: rs1124980; hg19: chr18-67548627;