18-69869260-C-T

Variant names:

• chr18-69869260-C-T
• rs12969657
• NM_001303618.2:c.831-1849G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303618.2(CD226):​c.831-1849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,020 control chromosomes in the GnomAD database, including 15,450 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 0.41 (15450 hom., cov: 33)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 24 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303618.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	NM_001303618.2	MANE Select	c.831-1849G>A		intron	N/A	NP_001290547.1	Q15762
	CD226	NM_006566.4		c.831-1849G>A		intron	N/A	NP_006557.2	Q15762
	CD226	NM_001303619.2		c.366-1849G>A		intron	N/A	NP_001290548.1	J3QR77

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	ENST00000582621.6	TSL:1 MANE Select	c.831-1849G>A		intron	N/A	ENSP00000461947.1	Q15762
	CD226	ENST00000280200.8	TSL:1	c.831-1849G>A		intron	N/A	ENSP00000280200.4	Q15762
	CD226	ENST00000581982.5	TSL:1	c.366-1849G>A		intron	N/A	ENSP00000464084.1	J3QR77

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62698 AN: 151902 Hom.: 15458 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.412 AC: 62685 AN: 152020 Hom.: 15450 Cov.: 33 AF XY: 0.419 AC XY: 31157 AN XY: 74300

African (AFR) AF: 0.125 AC: 5179 AN: 41476

American (AMR) AF: 0.510 AC: 7797 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1563 AN: 3470

East Asian (EAS) AF: 0.640 AC: 3301 AN: 5154

South Asian (SAS) AF: 0.487 AC: 2343 AN: 4808

European-Finnish (FIN) AF: 0.559 AC: 5898 AN: 10556

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35306 AN: 67948

Other (OTH) AF: 0.421 AC: 890 AN: 2114

Alfa AF: 0.468 Hom.: 2550

Bravo AF: 0.393

Asia WGS AF: 0.531 AC: 1844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.59
DANN	Benign	0.48
PhyloP100		-0.79
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: rs12969657; hg19: chr18-67536496;