9-133259834-C-T

Position:

• chr9-133259834-C-T

Variant summary

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

The NM_020469.3(ABO):​c.188G>A​(p.Arg63His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,612,996 control chromosomes in the GnomAD database, including 52,790 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.27 (5795 hom., cov: 33)
  • Exomes 𝑓: 0.25 (46995 hom.)
• Consequence: ABO NM_020469.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

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 (MetaRNN=0.0028227568).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.188G>A	p.Arg63His	missense_variant	4/8		NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.188G>A	p.Arg63His	missense_variant	4/9	5		ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40995 AN: 151954 Hom.: 5789 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.248 AC: 361927 AN: 1460924 Hom.: 46995 Cov.: 33 AF XY: 0.244 AC XY: 177517 AN XY: 726798

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.270 AC: 41021 AN: 152072 Hom.: 5795 Cov.: 33 AF XY: 0.269 AC XY: 19970 AN XY: 74352

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.252

Alfa AF: 0.246 Hom.: 8958

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.029
DEOGEN2	Benign	0.0067	T;.
LIST_S2	Benign	0.080	T;T
MetaRNN	Benign	0.0028	T;T
Sift4G	Benign	0.14	T;T
Vest4		0.10
gMVP		0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs549446; hg19: -;