rs8176741

Variant names:

• chr9-133256074-G-A
• rs8176741
• ENST00000611156.4:c.654C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-133256074-G-A
• chr9-133256074-G-C
• chr9-133256074-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000611156.4(ABO):​c.654C>T​(p.His218His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,588,890 control chromosomes in the GnomAD database, including 9,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1298 hom., cov: 33)
  • Exomes 𝑓: 0.089 (8127 hom.)
• Consequence: ABO ENST00000611156.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 81 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-0.194 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.668C>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.654C>T	p.His218His	synonymous_variant	Exon 8 of 8	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17529 AN: 151920 Hom.: 1296 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0740

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0798

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.119 AC: 24772 AN: 207772 AF XY: 0.127

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.0571

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.185

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.0775

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.0892 AC: 128163 AN: 1436852 Hom.: 8127 Cov.: 74 AF XY: 0.0948 AC XY: 67607 AN XY: 712938

African (AFR) AF: 0.166 AC: 5428 AN: 32778

American (AMR) AF: 0.0569 AC: 2274 AN: 39976

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3187 AN: 25596

East Asian (EAS) AF: 0.181 AC: 6883 AN: 37980

South Asian (SAS) AF: 0.260 AC: 21593 AN: 83082

European-Finnish (FIN) AF: 0.135 AC: 6968 AN: 51522

Middle Eastern (MID) AF: 0.150 AC: 862 AN: 5736

European-Non Finnish (NFE) AF: 0.0680 AC: 74860 AN: 1100708

Other (OTH) AF: 0.103 AC: 6108 AN: 59474

GnomAD4 genome AF: 0.115 AC: 17543 AN: 152038 Hom.: 1298 Cov.: 33 AF XY: 0.120 AC XY: 8883 AN XY: 74322

African (AFR) AF: 0.159 AC: 6569 AN: 41398

American (AMR) AF: 0.0741 AC: 1133 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3472

East Asian (EAS) AF: 0.183 AC: 942 AN: 5154

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4824

European-Finnish (FIN) AF: 0.137 AC: 1452 AN: 10612

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0798 AC: 5427 AN: 67972

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.0885 Hom.: 1708

Bravo AF: 0.106

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.86
PhyloP100		-0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8176741; hg19: chr9-136131461; COSMIC: COSV71743504;