rs8176722

Positions:

• chr9-133257367-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000538324.2(ABO):​c.371+42G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,611,700 control chromosomes in the GnomAD database, including 11,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1312 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10683 hom.)
• Consequence: ABO ENST00000538324.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.91).
• BP6: Variant 9-133257367-C-A is Benign according to our data. Variant chr9-133257367-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.371+42G>T		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.371+42G>T		intron_variant		5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18613 AN: 151884 Hom.: 1309 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.116

GnomAD3 exomes AF: 0.130 AC: 32419 AN: 248588 Hom.: 2751 AF XY: 0.138 AC XY: 18626 AN XY: 134824

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0652

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.183

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.0987

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.108 AC: 157995 AN: 1459698 Hom.: 10683 Cov.: 30 AF XY: 0.114 AC XY: 82542 AN XY: 726110

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0666

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.0903

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.123 AC: 18630 AN: 152002 Hom.: 1312 Cov.: 32 AF XY: 0.127 AC XY: 9432 AN XY: 74310

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0896

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.114

Alfa AF: 0.103 Hom.: 963

Bravo AF: 0.113

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs8176722; hg19: chr9-136132754;