9-133255635-C-T

Variant names:

• chr9-133255635-C-T
• rs8176751
• ENST00000453660.4:n.1125G>A

Variant summary

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

The ENST00000453660.4(ABO):​n.1125G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,563,090 control chromosomes in the GnomAD database, including 12,030 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 0.13 (1558 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10472 hom.)
• Consequence: ABO ENST00000453660.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 27 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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000453660.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	NR_198898.1		n.1107G>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	ENST00000453660.4	TSL:1	n.1125G>A		non_coding_transcript_exon	Exon 7 of 7
	ABO	ENST00000611156.4	TSL:5	c.*31G>A		3_prime_UTR	Exon 8 of 8	ENSP00000483265.1
	ABO	ENST00000538324.2	TSL:5	c.1089G>A	p.Pro363Pro	synonymous	Exon 9 of 9	ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19890 AN: 151760 Hom.: 1556 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.119

GnomAD2 exomes AF: 0.135 AC: 21981 AN: 163044 AF XY: 0.144

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.0672

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.0950

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.109 AC: 153222 AN: 1411210 Hom.: 10472 Cov.: 46 AF XY: 0.114 AC XY: 79359 AN XY: 697916

African (AFR) AF: 0.171 AC: 5471 AN: 32076

American (AMR) AF: 0.0687 AC: 2516 AN: 36646

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3265 AN: 25262

East Asian (EAS) AF: 0.180 AC: 6600 AN: 36708

South Asian (SAS) AF: 0.271 AC: 22005 AN: 81228

European-Finnish (FIN) AF: 0.155 AC: 7363 AN: 47388

Middle Eastern (MID) AF: 0.160 AC: 892 AN: 5572

European-Non Finnish (NFE) AF: 0.0901 AC: 98038 AN: 1087780

Other (OTH) AF: 0.121 AC: 7072 AN: 58550

GnomAD4 genome AF: 0.131 AC: 19903 AN: 151880 Hom.: 1558 Cov.: 32 AF XY: 0.135 AC XY: 9994 AN XY: 74262

African (AFR) AF: 0.166 AC: 6849 AN: 41322

American (AMR) AF: 0.0914 AC: 1398 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3468

East Asian (EAS) AF: 0.182 AC: 936 AN: 5152

South Asian (SAS) AF: 0.267 AC: 1284 AN: 4810

European-Finnish (FIN) AF: 0.154 AC: 1624 AN: 10576

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.102 AC: 6943 AN: 67948

Other (OTH) AF: 0.118 AC: 248 AN: 2110

Alfa AF: 0.127 Hom.: 530

Bravo AF: 0.122

Asia WGS AF: 0.206 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs8176751; hg19: chr9-136131022; COSMIC: COSV107533853;