rs727088

Variant names:

• chr18-69863203-G-A
• rs727088
• NM_001303618.2:c.*1111C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-69863203-G-A
• chr18-69863203-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 72 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=-0.98).
• 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 rank	MANE	Protein	UniProt
CD226	NM_001303618.2	c.*1111C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6	c.*1111C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001303618.2	ENSP00000461947.1
CD226	ENST00000280200.8	c.*1111C>T		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000280200.4
CD226	ENST00000581982.5	c.*1111C>T		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000464084.1
CD226	ENST00000578928.1	n.110-20808C>T		intron_variant	Intron 1 of 3	4		ENSP00000463152.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.333 AC: 2 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.302 AC: 12459 AN: 41234

American (AMR) AF: 0.540 AC: 8229 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3761 AN: 5160

South Asian (SAS) AF: 0.513 AC: 2463 AN: 4798

European-Finnish (FIN) AF: 0.583 AC: 6087 AN: 10440

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35599 AN: 67902

Other (OTH) AF: 0.467 AC: 981 AN: 2102

Alfa AF: 0.494 Hom.: 34697

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
PhyloP100		-0.74
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: rs727088; hg19: chr18-67530439; COSMIC: COSV54610887; COSMIC: COSV54610887;