chr9-133255801-C-T

Variant names:

• chr9-133255801-C-T
• rs8176749
• ENST00000611156.4:c.927G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000611156.4(ABO):​c.927G>A​(p.Leu309Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,613,552 control chromosomes in the GnomAD database, including 9,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1296 hom., cov: 32)
  • Exomes 𝑓: 0.089 (8291 hom.)
• Consequence: ABO ENST00000611156.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 116 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-1.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 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.941G>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	ENST00000611156.4	TSL:5	c.927G>A	p.Leu309Leu	synonymous	Exon 8 of 8	ENSP00000483265.1	A0A087X0C2
	ABO	ENST00000453660.4	TSL:1	n.959G>A		non_coding_transcript_exon	Exon 7 of 7
	ABO	ENST00000538324.2	TSL:5	c.927G>A	p.Leu309Leu	synonymous	Exon 8 of 9	ENSP00000483018.1	A0A087X009

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17485 AN: 151912 Hom.: 1294 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.117 AC: 29219 AN: 248690 AF XY: 0.125

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.0549

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.180

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.0778

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0893 AC: 130587 AN: 1461524 Hom.: 8291 Cov.: 65 AF XY: 0.0951 AC XY: 69134 AN XY: 727054

African (AFR) AF: 0.166 AC: 5544 AN: 33474

American (AMR) AF: 0.0557 AC: 2491 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 3251 AN: 26128

East Asian (EAS) AF: 0.175 AC: 6959 AN: 39698

South Asian (SAS) AF: 0.260 AC: 22394 AN: 86254

European-Finnish (FIN) AF: 0.136 AC: 7237 AN: 53296

Middle Eastern (MID) AF: 0.149 AC: 862 AN: 5768

European-Non Finnish (NFE) AF: 0.0680 AC: 75651 AN: 1111828

Other (OTH) AF: 0.103 AC: 6198 AN: 60370

GnomAD4 genome AF: 0.115 AC: 17498 AN: 152028 Hom.: 1296 Cov.: 32 AF XY: 0.119 AC XY: 8845 AN XY: 74322

African (AFR) AF: 0.159 AC: 6568 AN: 41396

American (AMR) AF: 0.0740 AC: 1131 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 463 AN: 3470

East Asian (EAS) AF: 0.180 AC: 933 AN: 5172

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4810

European-Finnish (FIN) AF: 0.136 AC: 1446 AN: 10600

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0796 AC: 5409 AN: 67976

Other (OTH) AF: 0.104 AC: 219 AN: 2112

Alfa AF: 0.0887 Hom.: 2935

Bravo AF: 0.106

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.6
DANN	Benign	0.83
PhyloP100		-1.5

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: rs8176749; hg19: chr9-136131188; COSMIC: COSV107533854;