rs4363269

chr9-133248453-A-G

Variant summary

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

The ENST00000679909.1(ABO):c.29-14844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,012 control chromosomes in the GnomAD database, including 5,252 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 0.21 (5252 hom., cov: 32)
• Consequence: ABO ENST00000679909.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000679909.1	c.29-14844T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31505 AN: 151894 Hom.: 5223 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0924

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.208 AC: 31581 AN: 152012 Hom.: 5252 Cov.: 32 AF XY: 0.206 AC XY: 15305 AN XY: 74306

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0924

Gnomad4 OTH AF: 0.191

Alfa AF: 0.167 Hom.: 841

Bravo AF: 0.222

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.2
Dann	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4363269; hg19: chr9-136123840;