dbSNP rs688976: ABO:p.Val36Phe (chr9-133261367-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000611156.4(ABO):c.106G>T(p.Val36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,594,332 control chromosomes in the GnomAD database, including 51,939 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 5809 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46130 hom. )

Consequence

ABO
ENST00000611156.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.461

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002935797).

BP6

Variant 9-133261367-C-A is Benign according to our data. Variant chr9-133261367-C-A is described in ClinVar as Benign. ClinVar VariationId is 769758.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1 link	n.118G>T		non_coding_transcript_exon_variant	Exon 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4 link	c.106G>T	p.Val36Phe	missense_variant	Exon 3 of 8	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41012

AN:

151998

Hom.:

5803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.384

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.254

GnomAD4 exome

AF:

0.248

AC:

357039

AN:

1442216

Hom.:

46130

Cov.:

AF XY:

0.244

AC XY:

174731

AN XY:

715164

show subpopulations

African (AFR)

AF:

0.310

AC:

10219

AN:

33006

American (AMR)

AF:

0.475

AC:

19940

AN:

42016

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

7192

AN:

25766

East Asian (EAS)

AF:

0.260

AC:

10094

AN:

38824

South Asian (SAS)

AF:

0.206

AC:

17035

AN:

82606

European-Finnish (FIN)

AF:

0.178

AC:

9290

AN:

52148

Middle Eastern (MID)

AF:

0.235

AC:

1352

AN:

5748

European-Non Finnish (NFE)

AF:

0.242

AC:

266546

AN:

1102372

Other (OTH)

AF:

0.257

AC:

15371

AN:

59730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

14341

28682

43024

57365

71706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9330

18660

27990

37320

46650

<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:

0.270

AC:

41039

AN:

152116

Hom.:

5809

Cov.:

AF XY:

0.269

AC XY:

19984

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.309

AC:

12816

AN:

41464

American (AMR)

AF:

0.385

AC:

5890

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

958

AN:

3472

East Asian (EAS)

AF:

0.271

AC:

1396

AN:

5160

South Asian (SAS)

AF:

0.215

AC:

1035

AN:

4822

European-Finnish (FIN)

AF:

0.178

AC:

1885

AN:

10604

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.241

AC:

16354

AN:

67982

Other (OTH)

AF:

0.253

AC:

535

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1541

3082

4622

6163

7704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.249

Hom.:

13152

Bravo

AF:

0.291

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.82

(source)

DEOGEN2

Benign

0.0018

T;.

LIST_S2

Benign

0.46

T;T

MetaRNN

Benign

0.0029

T;T

PhyloP100

-0.46

Sift4G

Benign

0.65

T;T

Vest4

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.41

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over