rs549446

Variant names:

• chr9-133259834-C-T
• rs549446
• ENST00000611156.4:c.188G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000611156.4(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. 4/5 in silico tools predict 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 (5795 hom., cov: 33)
  • Exomes 𝑓: 0.25 (46995 hom.)
• Consequence: ABO ENST00000611156.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 48 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000611156.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	NR_198898.1		n.200G>A		non_coding_transcript_exon	Exon 4 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	ENST00000611156.4	TSL:5	c.188G>A	p.Arg63His	missense	Exon 4 of 8	ENSP00000483265.1	A0A087X0C2
	ABO	ENST00000453660.4	TSL:1	n.218G>A		non_coding_transcript_exon	Exon 4 of 7
	ABO	ENST00000538324.2	TSL:5	c.188G>A	p.Arg63His	missense	Exon 4 of 9	ENSP00000483018.1	A0A087X009

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

African (AFR) AF: 0.309 AC: 10340 AN: 33462

American (AMR) AF: 0.476 AC: 21249 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 7287 AN: 26122

East Asian (EAS) AF: 0.259 AC: 10301 AN: 39696

South Asian (SAS) AF: 0.205 AC: 17702 AN: 86226

European-Finnish (FIN) AF: 0.178 AC: 9513 AN: 53364

Middle Eastern (MID) AF: 0.236 AC: 1359 AN: 5768

European-Non Finnish (NFE) AF: 0.242 AC: 268654 AN: 1111256

Other (OTH) AF: 0.257 AC: 15522 AN: 60356

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

African (AFR) AF: 0.309 AC: 12817 AN: 41466

American (AMR) AF: 0.385 AC: 5886 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1392 AN: 5164

South Asian (SAS) AF: 0.214 AC: 1034 AN: 4826

European-Finnish (FIN) AF: 0.178 AC: 1886 AN: 10586

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.241 AC: 16350 AN: 67970

Other (OTH) AF: 0.252 AC: 532 AN: 2108

Alfa AF: 0.253 Hom.: 13641

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
CADD	Benign	0.029
DEOGEN2	Benign	0.0067	T
LIST_S2	Benign	0.080	T
MetaRNN	Benign	0.0028	T
PhyloP100		-2.4
Sift4G	Benign	0.14	T
Vest4		0.10
gMVP		0.31

Splicing

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

Other links and lift over

dbSNP: rs549446;