rs11244053

Positions:

• chr9-133253973-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.*1693T>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 0.267 in 151,988 control chromosomes in the GnomAD database, including 5,817 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 0.27 (5817 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ABO NM_020469.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.*1693T>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.2787T>C		non_coding_transcript_exon_variant	7/7	1
ABO	ENST00000679909.1	c.29-20364T>C		intron_variant				ENSP00000506089
ABO	ENST00000647353.1	n.54-2821T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40471 AN: 151870 Hom.: 5801 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.257

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.267 AC: 40527 AN: 151988 Hom.: 5817 Cov.: 32 AF XY: 0.266 AC XY: 19779 AN XY: 74304

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.255

Alfa AF: 0.256 Hom.: 779

Bravo AF: 0.287

Asia WGS AF: 0.270 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11244053; hg19: chr9-136129360;