rs657152

Positions:

• chr9-133263862-A-C
• chr9-133263862-A-T

Variant summary

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

The NM_020469.3(ABO):​c.29-1694T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,100 control chromosomes in the GnomAD database, including 28,191 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 0.61 (28191 hom., cov: 33)
• Consequence: ABO NM_020469.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.29-1694T>G		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.29-1694T>G		intron_variant		5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92111 AN: 151982 Hom.: 28165 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.606 AC: 92180 AN: 152100 Hom.: 28191 Cov.: 33 AF XY: 0.604 AC XY: 44901 AN XY: 74340

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.619

Alfa AF: 0.624 Hom.: 49244

Bravo AF: 0.621

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs657152; hg19: chr9-136139265;