rs8176704

Positions:

• chr9-133260148-G-A

Variant summary

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

The NM_020469.3(ABO):​c.156-282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 152,280 control chromosomes in the GnomAD database, including 318 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 0.061 (318 hom., cov: 33)
• Consequence: ABO NM_020469.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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]

ABO (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.156-282C>T		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.156-282C>T		intron_variant		5		ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9321 AN: 152162 Hom.: 318 Cov.: 33

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0417

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0612 AC: 9325 AN: 152280 Hom.: 318 Cov.: 33 AF XY: 0.0623 AC XY: 4641 AN XY: 74454

Gnomad4 AFR AF: 0.0548

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0672

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0620 Hom.: 239

Bravo AF: 0.0554

Asia WGS AF: 0.0200 AC: 69 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	0.49
DANN	Benign	0.48
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: rs8176704; hg19: chr9-136135552;