Genetic Variant ABO:p.Leu309Leu (chr9-133255801-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000611156.4(ABO):c.927G>A(p.Leu309Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,613,552 control chromosomes in the GnomAD database, including 9,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1296 hom., cov: 32)

Exomes 𝑓: 0.089 ( 8291 hom. )

Consequence

ABO
ENST00000611156.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

116 publications found

Variant links:

Genes affected

ABO (HGNC:79): (ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase) This gene encodes proteins related to the first discovered blood group system, ABO. Variation in the ABO gene (chromosome 9q34.2) is the basis of the ABO blood group, thus the presence of an allele determines the blood group in an individual. The 'O' blood group is caused by a deletion of guanine-258 near the N-terminus of the protein which results in a frameshift and translation of an almost entirely different protein. Individuals with the A, B, and AB alleles express glycosyltransferase activities that convert the H antigen into the A or B antigen. Other minor alleles have been found for this gene. [provided by RefSeq, Apr 2022]

ABO links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP7

Synonymous conserved (PhyloP=-1.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1 link	n.941G>A		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4 link	c.927G>A	p.Leu309Leu	synonymous_variant	Exon 8 of 8	5		ENSP00000483265.1		A0A087X0C2

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17485

AN:

151912

Hom.:

1294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0739

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0795

Gnomad OTH

AF:

0.105

GnomAD2 exomes

AF:

0.117

AC:

29219

AN:

248690

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.0549

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.0778

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0893

AC:

130587

AN:

1461524

Hom.:

8291

Cov.:

AF XY:

0.0951

AC XY:

69134

AN XY:

727054

show subpopulations

African (AFR)

AF:

0.166

AC:

5544

AN:

33474

American (AMR)

AF:

0.0557

AC:

2491

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3251

AN:

26128

East Asian (EAS)

AF:

0.175

AC:

6959

AN:

39698

South Asian (SAS)

AF:

0.260

AC:

22394

AN:

86254

European-Finnish (FIN)

AF:

0.136

AC:

7237

AN:

53296

Middle Eastern (MID)

AF:

0.149

AC:

862

AN:

5768

European-Non Finnish (NFE)

AF:

0.0680

AC:

75651

AN:

1111828

Other (OTH)

AF:

0.103

AC:

6198

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

8628

17255

25883

34510

43138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.115

AC:

17498

AN:

152028

Hom.:

1296

Cov.:

AF XY:

0.119

AC XY:

8845

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.159

AC:

6568

AN:

41396

American (AMR)

AF:

0.0740

AC:

1131

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

463

AN:

3470

East Asian (EAS)

AF:

0.180

AC:

933

AN:

5172

South Asian (SAS)

AF:

0.256

AC:

1232

AN:

4810

European-Finnish (FIN)

AF:

0.136

AC:

1446

AN:

10600

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0796

AC:

5409

AN:

67976

Other (OTH)

AF:

0.104

AC:

219

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

791

1583

2374

3166

3957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0887

Hom.:

2935

Bravo

AF:

0.106

Asia WGS

AF:

0.195

AC:

679

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.6

(source)

DANN

Benign

0.83

PhyloP100

-1.5

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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9-133255801-C-T

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