9-133257486-T-C

Variant summary

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

The ENST00000538324.2(ABO):c.294A>G(p.Thr98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,612,622 control chromosomes in the GnomAD database, including 108,236 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). Synonymous variant affecting the same amino acid position (i.e. T98T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.40 (12422 hom., cov: 31)
  • Exomes 𝑓: 0.36 (95814 hom.)
• Consequence: ABO ENST00000538324.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-0.87).
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.294A>G	p.Thr98=	synonymous_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.294A>G	p.Thr98=	synonymous_variant	7/9	5		A2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60103 AN: 151066 Hom.: 12399 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.377

GnomAD3 exomes AF: 0.404 AC: 100688 AN: 249194 Hom.: 21539 AF XY: 0.399 AC XY: 53910 AN XY: 135200

Gnomad AFR exome AF: 0.470

Gnomad AMR exome AF: 0.557

Gnomad ASJ exome AF: 0.403

Gnomad EAS exome AF: 0.448

Gnomad SAS exome AF: 0.475

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.378

GnomAD4 exome AF: 0.356 AC: 520743 AN: 1461438 Hom.: 95814 Cov.: 40 AF XY: 0.358 AC XY: 260430 AN XY: 727008

Gnomad4 AFR exome AF: 0.465

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.398 AC: 60160 AN: 151184 Hom.: 12422 Cov.: 31 AF XY: 0.401 AC XY: 29632 AN XY: 73858

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.374

Alfa AF: 0.364 Hom.: 13744

Bravo AF: 0.408

Asia WGS AF: 0.472 AC: 1640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.6
Dann	Benign	0.37
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3

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: rs8176720; hg19: chr9-136132873; COSMIC: COSV71743463;