Genetic Variant ENST00000611156.4:c.768C>T (chr9-133255960-G-A) – 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.768C>T(p.Pro256Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,603,476 control chromosomes in the GnomAD database, including 50,441 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 0.25 ( 5105 hom., cov: 32)

Exomes 𝑓: 0.24 ( 45336 hom. )

Consequence

ABO
ENST00000611156.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.163

Publications

50 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=-0.85).

BP7

Synonymous conserved (PhyloP=-0.163 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1 link	n.782C>T		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.768C>T	p.Pro256Pro	synonymous_variant	Exon 8 of 8	5		ENSP00000483265.1		A0A087X0C2

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37972

AN:

151620

Hom.:

5099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.244

GnomAD2 exomes

AF:

0.270

AC:

61221

AN:

227146

AF XY:

0.258

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.489

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.244

AC:

354682

AN:

1451740

Hom.:

45336

Cov.:

AF XY:

0.241

AC XY:

174030

AN XY:

721458

show subpopulations

African (AFR)

AF:

0.242

AC:

8013

AN:

33180

American (AMR)

AF:

0.472

AC:

20169

AN:

42758

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

7216

AN:

25892

East Asian (EAS)

AF:

0.260

AC:

10177

AN:

39100

South Asian (SAS)

AF:

0.205

AC:

17416

AN:

85132

European-Finnish (FIN)

AF:

0.178

AC:

9393

AN:

52718

Middle Eastern (MID)

AF:

0.232

AC:

1337

AN:

5752

European-Non Finnish (NFE)

AF:

0.240

AC:

265843

AN:

1107246

Other (OTH)

AF:

0.252

AC:

15118

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

16874

33748

50622

67496

84370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9264

18528

27792

37056

46320

<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:

0.250

AC:

37994

AN:

151736

Hom.:

5105

Cov.:

AF XY:

0.250

AC XY:

18577

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.243

AC:

10039

AN:

41290

American (AMR)

AF:

0.380

AC:

5801

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

957

AN:

3468

East Asian (EAS)

AF:

0.266

AC:

1365

AN:

5122

South Asian (SAS)

AF:

0.211

AC:

1012

AN:

4804

European-Finnish (FIN)

AF:

0.178

AC:

1888

AN:

10590

Middle Eastern (MID)

AF:

0.247

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.239

AC:

16253

AN:

67886

Other (OTH)

AF:

0.243

AC:

513

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1387

2775

4162

5550

6937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.247

Hom.:

11125

Bravo

AF:

0.269

Asia WGS

AF:

0.262

AC:

908

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.8

(source)

DANN

Benign

0.64

PhyloP100

-0.16

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