9-133256234-GT-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000538324.2(ABO):c.493del(p.Thr165ProfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,613,214 control chromosomes in the GnomAD database, including 32 homozygotes. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (31 hom.)
• Consequence: ABO ENST00000538324.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome at 6 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.493del	p.Thr165ProfsTer26	frameshift_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.493del	p.Thr165ProfsTer26	frameshift_variant	8/9	5		A2

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 289 AN: 152162 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00279

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00325 AC: 797 AN: 245280 Hom.: 6 AF XY: 0.00398 AC XY: 533 AN XY: 133928

Gnomad AFR exome AF: 0.000200

Gnomad AMR exome AF: 0.000698

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0150

Gnomad FIN exome AF: 0.000372

Gnomad NFE exome AF: 0.00259

Gnomad OTH exome AF: 0.00317

GnomAD4 exome AF: 0.00334 AC: 4875 AN: 1460934 Hom.: 31 Cov.: 76 AF XY: 0.00373 AC XY: 2714 AN XY: 726780

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0146

Gnomad4 FIN exome AF: 0.000303

Gnomad4 NFE exome AF: 0.00296

Gnomad4 OTH exome AF: 0.00366

GnomAD4 genome AF: 0.00191 AC: 291 AN: 152280 Hom.: 1 Cov.: 33 AF XY: 0.00197 AC XY: 147 AN XY: 74450

Gnomad4 AFR AF: 0.000458

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00279

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000693 Hom.: 0

Bravo AF: 0.00174

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs563704490; hg19: chr9-136131621;