rs8176741

chr9-133256074-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000538324.2(ABO):c.654C>T(p.His218=) 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 ENST00000538324.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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 -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/exons	MANE	UniProt
ABO	NM_020469.3	c.654C>T	p.His218=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.654C>T	p.His218=	synonymous_variant	8/9	5		A2

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

GnomAD3 exomes AF: 0.119 AC: 24772 AN: 207772 Hom.: 2086 AF XY: 0.127 AC XY: 14330 AN XY: 112824

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 SAS exome AF: 0.263

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

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0569

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.0680

Gnomad4 OTH exome AF: 0.103

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

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0741

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0798

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0810 Hom.: 1041

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
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

Publications

LitVar

Other links and lift over

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