9-133264214-C-T

Variant names:

• chr9-133264214-C-T
• rs474279
• ENST00000611156.4:c.29-2046G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000611156.4(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 ENST00000611156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.41-2046G>A		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.29-2046G>A		intron_variant	Intron 1 of 7	5		ENSP00000483265.1

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

African (AFR) AF: 0.289 AC: 11983 AN: 41412

American (AMR) AF: 0.382 AC: 5828 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1462 AN: 5164

South Asian (SAS) AF: 0.213 AC: 1024 AN: 4808

European-Finnish (FIN) AF: 0.178 AC: 1883 AN: 10568

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16257 AN: 67964

Other (OTH) AF: 0.249 AC: 523 AN: 2100

Alfa AF: 0.245 Hom.: 15886

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
PhyloP100		-0.38
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

Other links and lift over

dbSNP: rs474279; hg19: chr9-136139617;