9-133266772-C-T

Position:

• chr9-133266772-C-T

Variant summary

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

The ENST00000538324.2(ABO):​c.29-4604G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 151,998 control chromosomes in the GnomAD database, including 896 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)
• Consequence: ABO ENST00000538324.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.29-4604G>A		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.29-4604G>A		intron_variant		5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15275 AN: 151880 Hom.: 892 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.0968

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15306 AN: 151998 Hom.: 896 Cov.: 31 AF XY: 0.106 AC XY: 7862 AN XY: 74310

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0795

Gnomad4 OTH AF: 0.0958

Alfa AF: 0.0533 Hom.: 59

Bravo AF: 0.0896

Asia WGS AF: 0.189 AC: 654 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.98
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8176672; hg19: chr9-136142185;