rs8176694

Variant names:

• chr9-133262243-T-C
• rs8176694
• ENST00000611156.4:c.29-75A>G

Variant summary

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

The ENST00000611156.4(ABO):​c.29-75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,306,704 control chromosomes in the GnomAD database, including 18,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (1672 hom., cov: 31)
  • Exomes 𝑓: 0.17 (17144 hom.)
• Consequence: ABO ENST00000611156.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.314
• Publications: 14 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 (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.41-75A>G		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.29-75A>G		intron_variant	Intron 1 of 7	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21577 AN: 152052 Hom.: 1676 Cov.: 31

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.168 AC: 193905 AN: 1154534 Hom.: 17144 AF XY: 0.167 AC XY: 97156 AN XY: 582616

African (AFR) AF: 0.0868 AC: 2348 AN: 27040

American (AMR) AF: 0.123 AC: 4480 AN: 36484

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5111 AN: 23630

East Asian (EAS) AF: 0.0844 AC: 3036 AN: 35976

South Asian (SAS) AF: 0.143 AC: 10706 AN: 74862

European-Finnish (FIN) AF: 0.115 AC: 5733 AN: 50010

Middle Eastern (MID) AF: 0.176 AC: 920 AN: 5222

European-Non Finnish (NFE) AF: 0.180 AC: 153175 AN: 851094

Other (OTH) AF: 0.167 AC: 8396 AN: 50216

GnomAD4 genome AF: 0.142 AC: 21573 AN: 152170 Hom.: 1672 Cov.: 31 AF XY: 0.139 AC XY: 10353 AN XY: 74398

African (AFR) AF: 0.0933 AC: 3874 AN: 41516

American (AMR) AF: 0.131 AC: 1996 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3472

East Asian (EAS) AF: 0.0513 AC: 265 AN: 5168

South Asian (SAS) AF: 0.153 AC: 737 AN: 4824

European-Finnish (FIN) AF: 0.117 AC: 1241 AN: 10598

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12274 AN: 67984

Other (OTH) AF: 0.145 AC: 305 AN: 2108

Alfa AF: 0.168 Hom.: 3908

Bravo AF: 0.140

Asia WGS AF: 0.120 AC: 414 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Three Vessel Coronary Disease Uncertain:1

-

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.55
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8176694; hg19: chr9-136137646;