dbSNP rs57743896: CD226:c.46+63G>A (chr18-69947298-C-T) – 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.46+63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0088 in 1,107,846 control chromosomes in the GnomAD database, including 75 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 0.0072 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 71 hom. )

Consequence

CD226
NM_001303618.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

Publications

3 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=-0.86).

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00905 (8652/955712) while in subpopulation MID AF = 0.0246 (96/3902). AF 95% confidence interval is 0.0206. There are 71 homozygotes in GnomAdExome4. There are 4433 alleles in the male GnomAdExome4 subpopulation. Median coverage is 12. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD226	NM_001303618.2 link	c.46+63G>A		intron_variant	Intron 1 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.46+63G>A		intron_variant	Intron 1 of 5	1	NM_001303618.2	ENSP00000461947.1		Q15762

Frequencies

GnomAD3 genomes

AF:

0.00720

AC:

1095

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00609

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00852

Gnomad FIN

AF:

0.00444

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00934

Gnomad OTH

AF:

0.00957

GnomAD4 exome

AF:

0.00905

AC:

8652

AN:

955712

Hom.:

Cov.:

AF XY:

0.00900

AC XY:

4433

AN XY:

492630

show subpopulations

African (AFR)

AF:

0.00703

AC:

154

AN:

21904

American (AMR)

AF:

0.00398

AC:

115

AN:

28930

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

118

AN:

19502

East Asian (EAS)

AF:

0.00

AC:

AN:

37226

South Asian (SAS)

AF:

0.00960

AC:

632

AN:

65862

European-Finnish (FIN)

AF:

0.00681

AC:

348

AN:

51122

Middle Eastern (MID)

AF:

0.0246

AC:

AN:

3902

European-Non Finnish (NFE)

AF:

0.00993

AC:

6791

AN:

684224

Other (OTH)

AF:

0.00925

AC:

398

AN:

43040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

439

878

1316

1755

2194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

226

452

678

904

1130

<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:

0.00718

AC:

1093

AN:

152134

Hom.:

Cov.:

AF XY:

0.00715

AC XY:

532

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00607

AC:

252

AN:

41490

American (AMR)

AF:

0.00471

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00811

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00444

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00934

AC:

635

AN:

68004

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

120

179

239

299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00762

Hom.:

Bravo

AF:

0.00735

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.5

(source)

DANN

Benign

0.35

PhyloP100

0.52

PromoterAI

-0.025

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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