rs73970293

chr18-69873286-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001303618.2(CD226):c.728-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,036,848 control chromosomes in the GnomAD database, including 41 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 0.011 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (19 hom.)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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=-0.63).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1614/152176) while in subpopulation AFR AF= 0.0351 (1459/41518). AF 95% confidence interval is 0.0336. There are 22 homozygotes in gnomad4. There are 733 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD226	NM_001303618.2	c.728-40C>T		intron_variant		ENST00000582621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000582621.6	c.728-40C>T		intron_variant		1	NM_001303618.2	P1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1608 AN: 152058 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00544

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0101

GnomAD3 exomes AF: 0.00321 AC: 708 AN: 220756 Hom.: 12 AF XY: 0.00249 AC XY: 299 AN XY: 119858

Gnomad AFR exome AF: 0.0354

Gnomad AMR exome AF: 0.00346

Gnomad ASJ exome AF: 0.00499

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000830

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000267

Gnomad OTH exome AF: 0.00270

GnomAD4 exome AF: 0.00155 AC: 1374 AN: 884672 Hom.: 19 Cov.: 11 AF XY: 0.00136 AC XY: 625 AN XY: 460466

Gnomad4 AFR exome AF: 0.0351

Gnomad4 AMR exome AF: 0.00408

Gnomad4 ASJ exome AF: 0.00579

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.000221

Gnomad4 OTH exome AF: 0.00476

GnomAD4 genome AF: 0.0106 AC: 1614 AN: 152176 Hom.: 22 Cov.: 32 AF XY: 0.00985 AC XY: 733 AN XY: 74388

Gnomad4 AFR AF: 0.0351

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00997

Alfa AF: 0.00957 Hom.: 4

Bravo AF: 0.0124

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	13
Dann	Benign	0.84

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: rs73970293; hg19: chr18-67540522;