9-133261366-A-AC

Variant names:

• chr9-133261366-A-AC
• rs782544248
• ENST00000538324.2:c.106dupG

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

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
• Clinical Significance: Benign; Affects no assertion criteria provided B:1 O:1
• Conservation: PhyloP100: -0.461

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]

ACMG classification

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	c.106dupG	p.Val36GlyfsTer21	frameshift_variant	Exon 3 of 8		NP_065202.2

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000135 AC: 3 AN: 222192 Hom.: 0 AF XY: 0.00000837 AC XY: 1 AN XY: 119486

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: 6 AN: 1445212 Hom.: 0 Cov.: 33 AF XY: 0.00000558 AC XY: 4 AN XY: 716930

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.: 32

ClinVar

Significance: Benign; Affects

Submissions summary: Benign:1 Other:1

Revision: no assertion criteria provided

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

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

Other links and lift over

dbSNP: rs782544248; hg19: chr9-136136769;