Variant 9-133261366-A-AC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_020469.3(ABO):c.106dupG(p.Val36GlyfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,445,212 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign,Affects (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

ABO
NM_020469.3 frameshift

Scores

Not classified

Clinical Significance

Benign; Affects no assertion criteria provided B:1O:1

Conservation

PhyloP100: -0.461

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 9-133261366-A-AC is Benign according to our data. Variant chr9-133261366-A-AC is described in ClinVar as [Benign, Affects]. Clinvar id is 1185001.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NM_020469.3 link	c.106dupG	p.Val36GlyfsTer21	frameshift_variant	Exon 3 of 8		NP_065202.2	P16442A0A089QDC1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2 link	c.106dupG	p.Val36GlyfsTer21	frameshift_variant	Exon 3 of 9	5		ENSP00000483018.1		A0A087X009

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000135

AC:

AN:

222192

Hom.:

AF XY:

0.00000837

AC XY:

AN XY:

119486

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000415

AC:

AN:

1445212

Hom.:

Cov.:

AF XY:

0.00000558

AC XY:

AN XY:

716930

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000724

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign; Affects

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Severely weakened expression of A on erythrocytes

Benign:1

Jul 12, 2023

Division of Hematology and Transfusion Medicine, Lund University

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

ABO blood group system

Other:1

Nov 01, 2022

Australian Red Cross Blood Service

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: research

Sample has c.106delTinsGG present in cis with c.260_261insG. Predict either A(end) or possible A3 subgroup. Observed serology on Australian donor sample indicated the similarity to A3 subgroup, but weaker in reactivity with the antisera tested. However, no known ABO*A3 alleles are present and unable to perform further serology testing as donor has not returned. Additional samples received from Lok Samarpan Raktadan Kendra (Surat India) also carry this variant and display serological reactivity of A(end) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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