rs568203

chr9-133276029-C-Achr9-133276029-C-G

Variant summary

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

The 9-133276029-C-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,080 control chromosomes in the GnomAD database, including 5,079 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 0.25 (5079 hom., cov: 33)
• Consequence: ABO ENST00000651471.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000651471.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38360 AN: 151962 Hom.: 5075 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.252 AC: 38378 AN: 152080 Hom.: 5079 Cov.: 33 AF XY: 0.253 AC XY: 18797 AN XY: 74334

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.246

Alfa AF: 0.238 Hom.: 5940

Bravo AF: 0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.6

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs568203; hg19: chr9-136151445;