rs8176719

chr9-133257521-T-TC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_020469.3(ABO):c.259-1_259insG(p.Thr87AspfsTer107) variant causes a frameshift, splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,612,876 control chromosomes in the GnomAD database, including 106,427 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.35 (10022 hom., cov: 0)
  • Exomes 𝑓: 0.36 (96405 hom.)
• Consequence: ABO NM_020469.3 frameshift, splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.259-1_259insG	p.Thr87AspfsTer107	frameshift_variant, splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.259-1_259insG	p.Thr87AspfsTer107	frameshift_variant, splice_region_variant, intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53648 AN: 151592 Hom.: 10015 Cov.: 0

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.350

GnomAD3 exomes AF: 0.368 AC: 91421 AN: 248556 Hom.: 17695 AF XY: 0.379 AC XY: 51101 AN XY: 134836

Gnomad AFR exome AF: 0.310

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.430

Gnomad EAS exome AF: 0.375

Gnomad SAS exome AF: 0.455

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.363

GnomAD4 exome AF: 0.358 AC: 523814 AN: 1461166 Hom.: 96405 Cov.: 37 AF XY: 0.364 AC XY: 264432 AN XY: 726878

Gnomad4 AFR exome AF: 0.302

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.418

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.348

GnomAD4 genome AF: 0.354 AC: 53677 AN: 151710 Hom.: 10022 Cov.: 0 AF XY: 0.357 AC XY: 26462 AN XY: 74116

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.348

Alfa AF: 0.363 Hom.: 2033

Bravo AF: 0.333

Asia WGS AF: 0.395 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs8176719; hg19: chr9-136132908;