rs727088

chr18-69863203-G-Achr18-69863203-G-C

Variant summary

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

The NM_001303618.2(CD226):c.*1111C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,568 control chromosomes in the GnomAD database, including 18,136 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 0.47 (18134 hom., cov: 31)
  • Exomes 𝑓: 0.36 (2 hom.)
• Consequence: CD226 NM_001303618.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.737

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD226	NM_001303618.2	c.*1111C>T		3_prime_UTR_variant	6/6	ENST00000582621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD226	ENST00000582621.6	c.*1111C>T		3_prime_UTR_variant	6/6	1	NM_001303618.2	P1
CD226	ENST00000280200.8	c.*1111C>T		3_prime_UTR_variant	7/7	1		P1
CD226	ENST00000581982.5	c.*1111C>T		3_prime_UTR_variant	5/5	1
CD226	ENST00000578928.1	c.110-20808C>T		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.475 AC: 71969 AN: 151434 Hom.: 18138 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.357 AC: 5 AN: 14 Hom.: 2 Cov.: 0 AF XY: 0.417 AC XY: 5 AN XY: 12

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.475 AC: 71983 AN: 151554 Hom.: 18134 Cov.: 31 AF XY: 0.481 AC XY: 35657 AN XY: 74068

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.467

Alfa AF: 0.508 Hom.: 23456

Bravo AF: 0.460

Asia WGS AF: 0.588 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.1
Dann	Benign	0.54

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: rs727088; hg19: chr18-67530439; COSMIC: COSV54610887; COSMIC: COSV54610887;