rs2519093

Variant names:

• chr9-133266456-T-C
• rs2519093
• ENST00000538324.2:c.29-4288A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020469.3(ABO):​c.29-4288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 151,838 control chromosomes in the GnomAD database, including 52,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.83 (52811 hom., cov: 29)
• Consequence: ABO NM_020469.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.08

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NM_020469.3	c.29-4288A>G		intron_variant	Intron 1 of 7		NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.29-4288A>G		intron_variant	Intron 1 of 8	5		ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126233 AN: 151722 Hom.: 52745 Cov.: 29

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.826

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.832 AC: 126357 AN: 151838 Hom.: 52811 Cov.: 29 AF XY: 0.834 AC XY: 61896 AN XY: 74202

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.826

Alfa AF: 0.823 Hom.: 8923

Bravo AF: 0.837

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

ABO blood group system Other:1

May 01, 2021

Blood Transfusion Service Zurich, Swiss Red Cross

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

ABO blood group system, phenotype A1, diagnostic specificity for ABO*A1.01 and ABO*A1.02 blood group alleles (rs2519093 A allele, NG_006669.2:g.13759A) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2519093; hg19: chr9-136141870;