rs8176714

Positions:

• chr9-133257791-G-A

Variant summary

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

The NM_020469.3(ABO):​c.240-249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,964 control chromosomes in the GnomAD database, including 5,724 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 (5724 hom., cov: 33)
• Consequence: ABO NM_020469.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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]

ABO (HGNC:):

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 = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.240-249C>T		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.240-249C>T		intron_variant		5		ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40052 AN: 151846 Hom.: 5718 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.264 AC: 40073 AN: 151964 Hom.: 5724 Cov.: 33 AF XY: 0.264 AC XY: 19577 AN XY: 74268

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.256

Alfa AF: 0.255 Hom.: 783

Bravo AF: 0.287

Asia WGS AF: 0.271 AC: 941 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	3.0
DANN	Benign	0.40
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

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: rs8176714; hg19: chr9-136133178;