9-133257486-T-C

Variant names:

• chr9-133257486-T-C
• rs8176720
• ENST00000611156.4:c.294A>G

Variant summary

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

The ENST00000611156.4(ABO):​c.294A>G​(p.Thr98Thr) 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 ENST00000611156.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 122 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=-0.87).
• 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 rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.308A>G		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.294A>G	p.Thr98Thr	synonymous_variant	Exon 7 of 8	5		ENSP00000483265.1

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

GnomAD2 exomes AF: 0.404 AC: 100688 AN: 249194 AF XY: 0.399

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 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

African (AFR) AF: 0.465 AC: 15547 AN: 33466

American (AMR) AF: 0.544 AC: 24321 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 10685 AN: 26136

East Asian (EAS) AF: 0.441 AC: 17508 AN: 39694

South Asian (SAS) AF: 0.473 AC: 40818 AN: 86250

European-Finnish (FIN) AF: 0.333 AC: 17787 AN: 53392

Middle Eastern (MID) AF: 0.395 AC: 2277 AN: 5766

European-Non Finnish (NFE) AF: 0.332 AC: 369001 AN: 1111664

Other (OTH) AF: 0.378 AC: 22799 AN: 60360

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

African (AFR) AF: 0.462 AC: 18960 AN: 41076

American (AMR) AF: 0.478 AC: 7253 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1439 AN: 3462

East Asian (EAS) AF: 0.455 AC: 2330 AN: 5116

South Asian (SAS) AF: 0.481 AC: 2300 AN: 4786

European-Finnish (FIN) AF: 0.334 AC: 3494 AN: 10466

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23291 AN: 67810

Other (OTH) AF: 0.374 AC: 784 AN: 2098

Alfa AF: 0.370 Hom.: 20974

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
PhyloP100		-1.5
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

Other links and lift over

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