chr18-69896736-T-C

Variant names:

• chr18-69896736-T-C
• rs1788114
• NM_001303618.2:c.383-691A>G

Variant summary

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

The NM_001303618.2(CD226):​c.383-691A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,996 control chromosomes in the GnomAD database, including 18,611 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 0.48 (18611 hom., cov: 31)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• 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]

ENSG00000304227 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	NM_001303618.2	MANE Select	c.383-691A>G		intron	N/A	NP_001290547.1
	CD226	NM_006566.4		c.383-691A>G		intron	N/A	NP_006557.2
	CD226	NM_001303619.2		c.-83-691A>G		intron	N/A	NP_001290548.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	ENST00000582621.6	TSL:1 MANE Select	c.383-691A>G		intron	N/A	ENSP00000461947.1
	CD226	ENST00000280200.8	TSL:1	c.383-691A>G		intron	N/A	ENSP00000280200.4
	CD226	ENST00000581982.5	TSL:1	c.-83-691A>G		intron	N/A	ENSP00000464084.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72483 AN: 151878 Hom.: 18562 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.478 AC: 72607 AN: 151996 Hom.: 18611 Cov.: 31 AF XY: 0.468 AC XY: 34803 AN XY: 74288

African (AFR) AF: 0.649 AC: 26874 AN: 41428

American (AMR) AF: 0.430 AC: 6571 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1993 AN: 3468

East Asian (EAS) AF: 0.230 AC: 1190 AN: 5164

South Asian (SAS) AF: 0.454 AC: 2184 AN: 4806

European-Finnish (FIN) AF: 0.286 AC: 3028 AN: 10580

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28972 AN: 67958

Other (OTH) AF: 0.505 AC: 1067 AN: 2112

Alfa AF: 0.452 Hom.: 4415

Bravo AF: 0.498

Asia WGS AF: 0.356 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.68
PhyloP100		-1.6
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: rs1788114; hg19: chr18-67563972;