18-69958049-C-T

Variant names:

• chr18-69958049-C-T
• rs1539964
• ENST00000851210.1:c.-28+3543G>A

Variant summary

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

The ENST00000851210.1(CD226):​c.-28+3543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,008 control chromosomes in the GnomAD database, including 18,736 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 0.45 (18736 hom., cov: 31)
• Consequence: CD226 ENST00000851210.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 7 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000851210.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	ENST00000851210.1		c.-28+3543G>A		intron	N/A	ENSP00000521269.1
	CD226	ENST00000951224.1		c.-28+1357G>A		intron	N/A	ENSP00000621283.1
	CD226	ENST00000579496.5	TSL:5	c.-127+3543G>A		intron	N/A	ENSP00000463927.1	J3QQW1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68134 AN: 151890 Hom.: 18723 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.448 AC: 68157 AN: 152008 Hom.: 18736 Cov.: 31 AF XY: 0.456 AC XY: 33850 AN XY: 74298

African (AFR) AF: 0.112 AC: 4668 AN: 41496

American (AMR) AF: 0.539 AC: 8228 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1975 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3080 AN: 5152

South Asian (SAS) AF: 0.563 AC: 2711 AN: 4814

European-Finnish (FIN) AF: 0.667 AC: 7041 AN: 10554

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 39016 AN: 67936

Other (OTH) AF: 0.449 AC: 946 AN: 2108

Alfa AF: 0.536 Hom.: 37607

Bravo AF: 0.425

Asia WGS AF: 0.562 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.33
DANN	Benign	0.82
PhyloP100		-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1539964;

hg19: chr18-67625285;