rs1788227

Variant names:

• chr18-69874389-G-C
• rs1788227
• NM_001303618.2:c.728-1143C>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.728-1143C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 152,168 control chromosomes in the GnomAD database, including 803 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 0.061 (803 hom., cov: 32)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 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.728-1143C>G		intron	N/A	NP_001290547.1	Q15762
	CD226	NM_006566.4		c.728-1143C>G		intron	N/A	NP_006557.2	Q15762
	CD226	NM_001303619.2		c.263-1143C>G		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.728-1143C>G		intron	N/A	ENSP00000461947.1	Q15762
	CD226	ENST00000280200.8	TSL:1	c.728-1143C>G		intron	N/A	ENSP00000280200.4	Q15762
	CD226	ENST00000581982.5	TSL:1	c.263-1143C>G		intron	N/A	ENSP00000464084.1	J3QR77

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9187 AN: 152050 Hom.: 802 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.0471

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

GnomAD4 genome AF: 0.0605 AC: 9208 AN: 152168 Hom.: 803 Cov.: 32 AF XY: 0.0588 AC XY: 4376 AN XY: 74410

African (AFR) AF: 0.193 AC: 8014 AN: 41474

American (AMR) AF: 0.0303 AC: 464 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00932 AC: 45 AN: 4826

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00243 AC: 165 AN: 68010

Other (OTH) AF: 0.0466 AC: 98 AN: 2104

Alfa AF: 0.0484 Hom.: 63

Bravo AF: 0.0687

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		0.29
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: rs1788227; hg19: chr18-67541625;