9-133256050-C-T

Variant names:

• chr9-133256050-C-T
• rs8176742
• ENST00000611156.4:c.678G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000611156.4(ABO):​c.678G>A​(p.Pro226Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,584,234 control chromosomes in the GnomAD database, including 47,228 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 0.22 (4250 hom., cov: 33)
  • Exomes 𝑓: 0.24 (42978 hom.)
• Consequence: ABO ENST00000611156.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 44 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-1.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.692G>A		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.678G>A	p.Pro226Pro	synonymous_variant	Exon 8 of 8	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33859 AN: 151818 Hom.: 4245 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.229

GnomAD2 exomes AF: 0.245 AC: 49369 AN: 201662 AF XY: 0.234

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.244

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.239 AC: 342966 AN: 1432298 Hom.: 42978 Cov.: 78 AF XY: 0.237 AC XY: 168124 AN XY: 710358

African (AFR) AF: 0.139 AC: 4533 AN: 32654

American (AMR) AF: 0.447 AC: 17505 AN: 39138

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 7076 AN: 25544

East Asian (EAS) AF: 0.255 AC: 9604 AN: 37730

South Asian (SAS) AF: 0.201 AC: 16646 AN: 82704

European-Finnish (FIN) AF: 0.175 AC: 8972 AN: 51218

Middle Eastern (MID) AF: 0.229 AC: 1316 AN: 5736

European-Non Finnish (NFE) AF: 0.239 AC: 262808 AN: 1098262

Other (OTH) AF: 0.245 AC: 14506 AN: 59312

GnomAD4 genome AF: 0.223 AC: 33872 AN: 151936 Hom.: 4250 Cov.: 33 AF XY: 0.223 AC XY: 16581 AN XY: 74258

African (AFR) AF: 0.147 AC: 6072 AN: 41372

American (AMR) AF: 0.370 AC: 5652 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1371 AN: 5140

South Asian (SAS) AF: 0.209 AC: 1010 AN: 4822

European-Finnish (FIN) AF: 0.179 AC: 1895 AN: 10602

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16272 AN: 67940

Other (OTH) AF: 0.227 AC: 480 AN: 2110

Alfa AF: 0.238 Hom.: 8316

Bravo AF: 0.237

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.72
PhyloP100		-1.3
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

Other links and lift over

dbSNP: rs8176742; hg19: chr9-136131437; COSMIC: COSV71743415;