rs8176722

Variant names:

• chr9-133257367-C-A
• rs8176722
• ENST00000611156.4:c.371+42G>T

Variant summary

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

The ENST00000611156.4(ABO):​c.371+42G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,611,700 control chromosomes in the GnomAD database, including 11,995 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 0.12 (1312 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10683 hom.)
• Consequence: ABO ENST00000611156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 53 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.385+42G>T		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.371+42G>T		intron_variant	Intron 7 of 7	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18613 AN: 151884 Hom.: 1309 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.130 AC: 32419 AN: 248588 AF XY: 0.138

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0652

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.183

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.0987

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.108 AC: 157995 AN: 1459698 Hom.: 10683 Cov.: 30 AF XY: 0.114 AC XY: 82542 AN XY: 726110

African (AFR) AF: 0.140 AC: 4666 AN: 33382

American (AMR) AF: 0.0666 AC: 2977 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3399 AN: 26086

East Asian (EAS) AF: 0.183 AC: 7269 AN: 39664

South Asian (SAS) AF: 0.268 AC: 23083 AN: 86106

European-Finnish (FIN) AF: 0.155 AC: 8261 AN: 53330

Middle Eastern (MID) AF: 0.158 AC: 912 AN: 5764

European-Non Finnish (NFE) AF: 0.0903 AC: 100241 AN: 1110400

Other (OTH) AF: 0.119 AC: 7187 AN: 60282

GnomAD4 genome AF: 0.123 AC: 18630 AN: 152002 Hom.: 1312 Cov.: 32 AF XY: 0.127 AC XY: 9432 AN XY: 74310

African (AFR) AF: 0.135 AC: 5603 AN: 41358

American (AMR) AF: 0.0896 AC: 1371 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3472

East Asian (EAS) AF: 0.183 AC: 946 AN: 5166

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4820

European-Finnish (FIN) AF: 0.153 AC: 1617 AN: 10580

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6957 AN: 67996

Other (OTH) AF: 0.114 AC: 241 AN: 2108

Alfa AF: 0.106 Hom.: 2710

Bravo AF: 0.113

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.49
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs8176722; hg19: chr9-136132754; COSMIC: COSV107533956;