9-133276029-C-A

Variant names:

• chr9-133276029-C-A
• rs568203
• ENST00000651471.1:n.-5G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000651471.1(ABO):​n.-5G>T 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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000651471.1	n.-5G>T		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

African (AFR) AF: 0.247 AC: 10260 AN: 41478

American (AMR) AF: 0.374 AC: 5718 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3470

East Asian (EAS) AF: 0.282 AC: 1450 AN: 5146

South Asian (SAS) AF: 0.214 AC: 1035 AN: 4826

European-Finnish (FIN) AF: 0.193 AC: 2044 AN: 10606

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16252 AN: 67964

Other (OTH) AF: 0.246 AC: 519 AN: 2110

Alfa AF: 0.244 Hom.: 8475

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
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs568203; hg19: chr9-136151445;