rs8176682

Variant names:

• chr9-133263894-C-T
• rs8176682
• ENST00000611156.4:c.29-1726G>A

Variant summary

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

The ENST00000611156.4(ABO):​c.29-1726G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,162 control chromosomes in the GnomAD database, including 8,489 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 0.32 (8489 hom., cov: 33)
• Consequence: ABO ENST00000611156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• Publications: 16 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.41-1726G>A		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.29-1726G>A		intron_variant	Intron 1 of 7	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49328 AN: 152044 Hom.: 8476 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.324 AC: 49358 AN: 152162 Hom.: 8489 Cov.: 33 AF XY: 0.324 AC XY: 24090 AN XY: 74384

African (AFR) AF: 0.212 AC: 8794 AN: 41514

American (AMR) AF: 0.312 AC: 4767 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1737 AN: 5184

South Asian (SAS) AF: 0.337 AC: 1623 AN: 4812

European-Finnish (FIN) AF: 0.344 AC: 3641 AN: 10572

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26745 AN: 67998

Other (OTH) AF: 0.358 AC: 756 AN: 2114

Alfa AF: 0.374 Hom.: 36554

Bravo AF: 0.316

Asia WGS AF: 0.310 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.88
PhyloP100		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs8176682; hg19: chr9-136139297; COSMIC: COSV71743474;