rs8176717

Positions:

• chr9-133257647-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000538324.2(ABO):​c.240-105C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,391,948 control chromosomes in the GnomAD database, including 42,320 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 (5392 hom., cov: 32)
  • Exomes 𝑓: 0.24 (36928 hom.)
• Consequence: ABO ENST00000538324.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 -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 = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.240-105C>A		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.240-105C>A		intron_variant		5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39149 AN: 151800 Hom.: 5387 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.239 AC: 296211 AN: 1240030 Hom.: 36928 AF XY: 0.236 AC XY: 144663 AN XY: 612464

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.454

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.258 AC: 39169 AN: 151918 Hom.: 5392 Cov.: 32 AF XY: 0.257 AC XY: 19114 AN XY: 74264

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.246

Alfa AF: 0.253 Hom.: 4441

Bravo AF: 0.278

Asia WGS AF: 0.263 AC: 914 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	0.29
DANN	Benign	0.62
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs8176717; hg19: chr9-136133034; COSMIC: COSV71743436;