9-133273232-C-T

Variant names:

• chr9-133273232-C-T
• rs500498
• ENST00000611156.4:c.28+1930G>A

Variant summary

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

The ENST00000611156.4(ABO):​c.28+1930G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,474 control chromosomes in the GnomAD database, including 16,994 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 0.47 (16994 hom., cov: 31)
• Consequence: ABO ENST00000611156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 26 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.40+1930G>A		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.28+1930G>A		intron_variant	Intron 1 of 7	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71321 AN: 151358 Hom.: 16971 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.471 AC: 71381 AN: 151474 Hom.: 16994 Cov.: 31 AF XY: 0.472 AC XY: 34903 AN XY: 73966

African (AFR) AF: 0.505 AC: 20829 AN: 41244

American (AMR) AF: 0.574 AC: 8723 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1479 AN: 3464

East Asian (EAS) AF: 0.490 AC: 2511 AN: 5120

South Asian (SAS) AF: 0.443 AC: 2131 AN: 4808

European-Finnish (FIN) AF: 0.388 AC: 4069 AN: 10500

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.447 AC: 30284 AN: 67820

Other (OTH) AF: 0.469 AC: 990 AN: 2110

Alfa AF: 0.417 Hom.: 2907

Bravo AF: 0.493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

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

Other links and lift over

dbSNP: rs500498; hg19: chr9-136148647;