dbSNP rs73970293: CD226:c.728-40C>T (chr18-69873286-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.728-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,036,848 control chromosomes in the GnomAD database, including 41 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 0.011 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 19 hom. )

Consequence

CD226
NM_001303618.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.149

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=-0.63).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0106 (1614/152176) while in subpopulation AFR AF = 0.0351 (1459/41518). AF 95% confidence interval is 0.0336. There are 22 homozygotes in GnomAd4. There are 733 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD226	NM_001303618.2 link	c.728-40C>T		intron_variant	Intron 3 of 5	ENST00000582621.6	NP_001290547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD226	ENST00000582621.6 link	c.728-40C>T		intron_variant	Intron 3 of 5	1	NM_001303618.2	ENSP00000461947.1

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1608

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0351

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0101

GnomAD2 exomes

AF:

0.00321

AC:

708

AN:

220756

AF XY:

0.00249

show subpopulations

Gnomad AFR exome

AF:

0.0354

Gnomad AMR exome

AF:

0.00346

Gnomad ASJ exome

AF:

0.00499

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000267

Gnomad OTH exome

AF:

0.00270

GnomAD4 exome

AF:

0.00155

AC:

1374

AN:

884672

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

625

AN XY:

460466

show subpopulations

African (AFR)

AF:

0.0351

AC:

745

AN:

21236

American (AMR)

AF:

0.00408

AC:

148

AN:

36274

Ashkenazi Jewish (ASJ)

AF:

0.00579

AC:

126

AN:

21766

East Asian (EAS)

AF:

0.00

AC:

AN:

35672

South Asian (SAS)

AF:

0.000105

AC:

AN:

66358

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51812

Middle Eastern (MID)

AF:

0.00395

AC:

AN:

4560

European-Non Finnish (NFE)

AF:

0.000221

AC:

134

AN:

606064

Other (OTH)

AF:

0.00476

AC:

195

AN:

40930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

139

209

278

348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.0106

AC:

1614

AN:

152176

Hom.:

Cov.:

AF XY:

0.00985

AC XY:

733

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0351

AC:

1459

AN:

41518

American (AMR)

AF:

0.00543

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68008

Other (OTH)

AF:

0.00997

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

156

234

312

390

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:

0.00781

Hom.:

Bravo

AF:

0.0124

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.15

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