9-133272408-G-T

Position:

• chr9-133272408-G-T

Variant summary

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

The NM_020469.3(ABO):​c.28+2754C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,892 control chromosomes in the GnomAD database, including 17,182 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 0.47 (17182 hom., cov: 31)
• Consequence: ABO NM_020469.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.28+2754C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.28+2754C>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71695 AN: 151774 Hom.: 17158 Cov.: 31

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.472 AC: 71757 AN: 151892 Hom.: 17182 Cov.: 31 AF XY: 0.473 AC XY: 35134 AN XY: 74220

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.468

Alfa AF: 0.473 Hom.: 2149

Bravo AF: 0.493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs659104; hg19: chr9-136147823;