9-133255801-C-T

Variant summary

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

The ENST00000538324.2(ABO):c.927G>A(p.Leu309=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,613,552 control chromosomes in the GnomAD database, including 9,587 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 (1296 hom., cov: 32)
  • Exomes 𝑓: 0.089 (8291 hom.)
• Consequence: ABO ENST00000538324.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.62).
• BP7: Synonymous conserved (PhyloP=-1.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.927G>A	p.Leu309=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.927G>A	p.Leu309=	synonymous_variant	8/9	5		A2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17485 AN: 151912 Hom.: 1294 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.117 AC: 29219 AN: 248690 Hom.: 2409 AF XY: 0.125 AC XY: 16833 AN XY: 135052

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.0549

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.180

Gnomad SAS exome AF: 0.260

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.0778

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0893 AC: 130587 AN: 1461524 Hom.: 8291 Cov.: 65 AF XY: 0.0951 AC XY: 69134 AN XY: 727054

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0557

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.0680

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.115 AC: 17498 AN: 152028 Hom.: 1296 Cov.: 32 AF XY: 0.119 AC XY: 8845 AN XY: 74322

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0740

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0863 Hom.: 1914

Bravo AF: 0.106

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	5.6
Dann	Benign	0.83

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: rs8176749; hg19: chr9-136131188;