dbSNP rs62090790: CD226:c.831-61C>T (chr18-69867472-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001303618.2(CD226):c.831-61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,088,650 control chromosomes in the GnomAD database, including 511 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 0.027 ( 68 hom., cov: 32)

Exomes 𝑓: 0.028 ( 443 hom. )

Consequence

CD226
NM_001303618.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.268

Publications

2 publications found

Variant links:

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]

CD226 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0267 (4053/152056) while in subpopulation NFE AF = 0.0307 (2086/67996). AF 95% confidence interval is 0.0296. There are 68 homozygotes in GnomAd4. There are 1938 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 68 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD226	NM_001303618.2 link	c.831-61C>T		intron_variant	Intron 4 of 5	ENST00000582621.6	NP_001290547.1	Q15762

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6 link	c.831-61C>T		intron_variant	Intron 4 of 5	1	NM_001303618.2	ENSP00000461947.1		Q15762

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

4043

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0290

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0258

Gnomad FIN

AF:

0.0282

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0307

Gnomad OTH

AF:

0.0226

GnomAD4 exome

AF:

0.0276

AC:

25858

AN:

936594

Hom.:

443

AF XY:

0.0276

AC XY:

13490

AN XY:

489294

show subpopulations

African (AFR)

AF:

0.0318

AC:

750

AN:

23550

American (AMR)

AF:

0.0121

AC:

530

AN:

43834

Ashkenazi Jewish (ASJ)

AF:

0.00939

AC:

214

AN:

22796

East Asian (EAS)

AF:

0.00401

AC:

150

AN:

37440

South Asian (SAS)

AF:

0.0238

AC:

1795

AN:

75504

European-Finnish (FIN)

AF:

0.0285

AC:

1360

AN:

47740

Middle Eastern (MID)

AF:

0.0189

AC:

AN:

4768

European-Non Finnish (NFE)

AF:

0.0311

AC:

19805

AN:

637674

Other (OTH)

AF:

0.0269

AC:

1164

AN:

43288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1226

2452

3677

4903

6129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

564

1128

1692

2256

2820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0267

AC:

4053

AN:

152056

Hom.:

Cov.:

AF XY:

0.0261

AC XY:

1938

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0291

AC:

1208

AN:

41474

American (AMR)

AF:

0.0103

AC:

157

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3470

East Asian (EAS)

AF:

0.00251

AC:

AN:

5180

South Asian (SAS)

AF:

0.0260

AC:

125

AN:

4804

European-Finnish (FIN)

AF:

0.0282

AC:

297

AN:

10550

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0307

AC:

2086

AN:

67996

Other (OTH)

AF:

0.0223

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

206

412

619

825

1031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0257

Hom.:

Bravo

AF:

0.0255

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.3

(source)

DANN

Benign

0.39

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over