ENST00000611156.4:c.240-249C>T

Variant names:

• chr9-133257791-G-A
• rs8176714
• ENST00000611156.4:c.240-249C>T

Variant summary

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

The ENST00000611156.4(ABO):​c.240-249C>T 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 151,964 control chromosomes in the GnomAD database, including 5,724 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 (5724 hom., cov: 33)
• Consequence: ABO ENST00000611156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.252-249C>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.240-249C>T		intron_variant	Intron 5 of 7	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40052 AN: 151846 Hom.: 5718 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.264 AC: 40073 AN: 151964 Hom.: 5724 Cov.: 33 AF XY: 0.264 AC XY: 19577 AN XY: 74268

African (AFR) AF: 0.271 AC: 11209 AN: 41360

American (AMR) AF: 0.419 AC: 6392 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1450 AN: 5162

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4818

European-Finnish (FIN) AF: 0.184 AC: 1947 AN: 10580

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

European-Non Finnish (NFE) AF: 0.241 AC: 16372 AN: 67988

Other (OTH) AF: 0.256 AC: 539 AN: 2108

Alfa AF: 0.258 Hom.: 1733

Bravo AF: 0.287

Asia WGS AF: 0.271 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.40
PhyloP100		0.074
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

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

Other links and lift over

dbSNP: rs8176714; hg19: chr9-136133178;