rs8176742

chr9-133256050-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The ENST00000538324.2(ABO):c.678G>A(p.Pro226=) 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. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (4250 hom., cov: 33)
  • Exomes 𝑓: 0.24 (42978 hom.)
• Consequence: ABO ENST00000538324.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-133256050-C-T is Benign according to our data. Variant chr9-133256050-C-T is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
ABO	NM_020469.3	c.678G>A	p.Pro226=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.678G>A	p.Pro226=	synonymous_variant	8/9	5		A2

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

GnomAD3 exomes AF: 0.245 AC: 49369 AN: 201662 Hom.: 7081 AF XY: 0.234 AC XY: 25628 AN XY: 109470

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 SAS exome AF: 0.196

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

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.245

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

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.227

Alfa AF: 0.239 Hom.: 6252

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
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

Publications

LitVar

Other links and lift over

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