rs8176694

Positions:

• chr9-133262243-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000538324.2(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 ENST00000538324.2 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.314

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.29-75A>G		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.29-75A>G		intron_variant		5		ENSP00000483018	A2

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

Gnomad4 AFR exome AF: 0.0868

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.0844

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.167

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

Gnomad4 AFR AF: 0.0933

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0513

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.145

Alfa AF: 0.174 Hom.: 3127

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

Uncertain significance, no assertion criteria provided

clinical testing

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.55
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

Publications

LitVar

Other links and lift over

dbSNP: rs8176694; hg19: chr9-136137646;