9-133253159-A-G

Position:

• chr9-133253159-A-G

Variant summary

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

The NM_020469.3(ABO):​c.*2507T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,874 control chromosomes in the GnomAD database, including 34,465 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 0.67 (34463 hom., cov: 32)
  • Exomes 𝑓: 0.60 (2 hom.)
• Consequence: ABO NM_020469.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.*2507T>C		3_prime_UTR_variant	8/8		NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000453660.4	n.3601T>C		non_coding_transcript_exon_variant	7/7	1
ABO	ENST00000679909.1	c.29-19550T>C		intron_variant				ENSP00000506089
ABO	ENST00000647353.1	n.54-2007T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101484 AN: 151746 Hom.: 34425 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.640

GnomAD4 exome AF: 0.600 AC: 6 AN: 10 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.669 AC: 101566 AN: 151864 Hom.: 34463 Cov.: 32 AF XY: 0.670 AC XY: 49770 AN XY: 74244

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.637

Alfa AF: 0.619 Hom.: 17245

Bravo AF: 0.676

Asia WGS AF: 0.682 AC: 2371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.1
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7857390; hg19: chr9-136128546;