rs8176745

Positions:

• chr9-133255960-G-A

Variant summary

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

The ENST00000538324.2(ABO):​c.768C>T​(p.Pro256=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,603,476 control chromosomes in the GnomAD database, including 50,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.25 (5105 hom., cov: 32)
  • Exomes 𝑓: 0.24 (45336 hom.)
• Consequence: ABO ENST00000538324.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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=-0.85).
• BP6: Variant 9-133255960-G-A is Benign according to our data. Variant chr9-133255960-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.163 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.768C>T	p.Pro256=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.768C>T	p.Pro256=	synonymous_variant	8/9	5		A2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37972 AN: 151620 Hom.: 5099 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.270 AC: 61221 AN: 227146 Hom.: 9368 AF XY: 0.258 AC XY: 31941 AN XY: 123874

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.489

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.266

Gnomad SAS exome AF: 0.207

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.244 AC: 354682 AN: 1451740 Hom.: 45336 Cov.: 73 AF XY: 0.241 AC XY: 174030 AN XY: 721458

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.250 AC: 37994 AN: 151736 Hom.: 5105 Cov.: 32 AF XY: 0.250 AC XY: 18577 AN XY: 74162

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.243

Alfa AF: 0.246 Hom.: 8159

Bravo AF: 0.269

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.64

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: rs8176745; hg19: chr9-136131347; COSMIC: COSV71743414;