rs574347

Positions:

• chr9-133260255-T-C

Variant summary

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

The ENST00000538324.2(ABO):​c.156-389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,176 control chromosomes in the GnomAD database, including 5,831 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 0.27 (5831 hom., cov: 33)
• Consequence: ABO ENST00000538324.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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 (Cadd=0.929).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.156-389A>G		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.156-389A>G		intron_variant		5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41062 AN: 152058 Hom.: 5825 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.270 AC: 41088 AN: 152176 Hom.: 5831 Cov.: 33 AF XY: 0.269 AC XY: 20009 AN XY: 74402

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.253

Alfa AF: 0.251 Hom.: 6498

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs574347; hg19: -;