Variant 9-133255928-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020469.3(ABO):c.800G>C(p.Gly267Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,612,132 control chromosomes in the GnomAD database, including 9,548 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G267R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.11 ( 1265 hom., cov: 32)

Exomes 𝑓: 0.089 ( 8283 hom. )

Consequence

ABO
NM_020469.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.517

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:

ABO (HGNC:):

ABO links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048752427).

BP6

Variant 9-133255928-C-G is Benign according to our data. Variant chr9-133255928-C-G is described in ClinVar as [Benign]. Clinvar id is 242740.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-133255928-C-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ABO	NM_020469.3 linkuse as main transcript	c.800G>C	p.Gly267Ala	missense_variant	8/8		NP_065202.2	P16442A0A089QDC1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2 linkuse as main transcript	c.800G>C	p.Gly267Ala	missense_variant	8/9	5		ENSP00000483018.1		A0A087X009

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17433

AN:

151762

Hom.:

1263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.0736

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.0801

Gnomad NFE

AF:

0.0795

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.118

AC:

28678

AN:

243428

Hom.:

2310

AF XY:

0.125

AC XY:

16600

AN XY:

132554

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.0552

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.182

Gnomad SAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.0777

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0895

AC:

130626

AN:

1460250

Hom.:

8283

Cov.:

AF XY:

0.0952

AC XY:

69147

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.0556

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.180

Gnomad4 SAS exome

AF:

0.259

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.0681

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.115

AC:

17446

AN:

151882

Hom.:

1265

Cov.:

AF XY:

0.119

AC XY:

8821

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.0737

Gnomad4 ASJ

AF:

0.134

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.0796

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0955

Hom.:

296

Bravo

AF:

0.106

TwinsUK

AF:

0.0615

AC:

228

ALSPAC

AF:

0.0576

AC:

222

ESP6500AA

AF:

0.154

AC:

605

ESP6500EA

AF:

0.0736

AC:

608

ExAC

AF:

0.118

AC:

14311

Asia WGS

AF:

0.197

AC:

683

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Three Vessel Coronary Disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Benign

0.0020

DANN

Benign

0.40

DEOGEN2

Benign

0.025

T;.

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.45

T;T

MetaRNN

Benign

0.0049

T;T

PrimateAI

Benign

0.43

Sift4G

Benign

1.0

T;T

Vest4

0.055

GERP RS

-8.4

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over