9-133264214-C-T

Position:

• chr9-133264214-C-T

Variant summary

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

The NM_020469.3(ABO):​c.29-2046G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,960 control chromosomes in the GnomAD database, including 5,546 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 0.26 (5546 hom., cov: 32)
• Consequence: ABO NM_020469.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.29-2046G>A		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.29-2046G>A		intron_variant		5		ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40058 AN: 151842 Hom.: 5540 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.264 AC: 40081 AN: 151960 Hom.: 5546 Cov.: 32 AF XY: 0.263 AC XY: 19547 AN XY: 74294

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.249

Alfa AF: 0.236 Hom.: 5826

Bravo AF: 0.284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs474279; hg19: chr9-136139617;