rs8176681

Variant names:

• chr9-133264351-T-C
• rs8176681
• ENST00000611156.4:c.29-2183A>G

Variant summary

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

The ENST00000611156.4(ABO):​c.29-2183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,170 control chromosomes in the GnomAD database, including 9,497 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 0.34 (9497 hom., cov: 33)
• Consequence: ABO ENST00000611156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• Publications: 21 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.41-2183A>G		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.29-2183A>G		intron_variant	Intron 1 of 7	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52328 AN: 152052 Hom.: 9486 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.344 AC: 52360 AN: 152170 Hom.: 9497 Cov.: 33 AF XY: 0.343 AC XY: 25488 AN XY: 74376

African (AFR) AF: 0.233 AC: 9678 AN: 41542

American (AMR) AF: 0.330 AC: 5046 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1007 AN: 3464

East Asian (EAS) AF: 0.334 AC: 1730 AN: 5184

South Asian (SAS) AF: 0.346 AC: 1669 AN: 4830

European-Finnish (FIN) AF: 0.360 AC: 3802 AN: 10562

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28291 AN: 67992

Other (OTH) AF: 0.375 AC: 788 AN: 2104

Alfa AF: 0.380 Hom.: 5931

Bravo AF: 0.337

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.35
PhyloP100		0.44

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: rs8176681; hg19: chr9-136139754; COSMIC: COSV71743475;