rs505922

Positions:

• chr9-133273813-C-T

Variant summary

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

The ENST00000538324.2(ABO):​c.28+1349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,990 control chromosomes in the GnomAD database, including 31,838 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31838 hom., cov: 31)
• Consequence: ABO ENST00000538324.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.28+1349G>A		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.28+1349G>A		intron_variant		5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97949 AN: 151872 Hom.: 31808 Cov.: 31

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.645 AC: 98024 AN: 151990 Hom.: 31838 Cov.: 31 AF XY: 0.642 AC XY: 47716 AN XY: 74294

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.655

Alfa AF: 0.650 Hom.: 42754

Bravo AF: 0.663

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs505922; hg19: chr9-136149229;