rs643434

chr9-133266942-A-Gchr9-133266942-A-T

Variant summary

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

The NM_020469.3(ABO):c.29-4774T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,002 control chromosomes in the GnomAD database, including 27,728 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 0.60 (27728 hom., cov: 31)
• Consequence: ABO NM_020469.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.29-4774T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.29-4774T>C		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91258 AN: 151884 Hom.: 27706 Cov.: 31

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.601 AC: 91321 AN: 152002 Hom.: 27728 Cov.: 31 AF XY: 0.599 AC XY: 44524 AN XY: 74278

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.618

Alfa AF: 0.612 Hom.: 25924

Bravo AF: 0.615

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs643434; hg19: chr9-136142355;