rs8176693

Positions:

• chr9-133262254-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000538324.2(ABO):​c.29-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0942 in 1,184,454 control chromosomes in the GnomAD database, including 7,340 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (896 hom., cov: 31)
  • Exomes 𝑓: 0.093 (6444 hom.)
• Consequence: ABO ENST00000538324.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.29-86G>A		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.29-86G>A		intron_variant		5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15303 AN: 152064 Hom.: 893 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0707

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.0958

GnomAD4 exome AF: 0.0933 AC: 96297 AN: 1032272 Hom.: 6444 AF XY: 0.100 AC XY: 52661 AN XY: 525058

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0547

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.0699

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.101 AC: 15324 AN: 152182 Hom.: 896 Cov.: 31 AF XY: 0.106 AC XY: 7875 AN XY: 74396

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0708

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0948

Alfa AF: 0.0913 Hom.: 176

Bravo AF: 0.0898

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.36

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: rs8176693; hg19: chr9-136137657; COSMIC: COSV71743612;