rs8176746

Variant names:

• chr9-133255935-G-T
• rs8176746
• ENST00000611156.4:c.793C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-133255935-G-T
• chr9-133255935-G-A
• chr9-133255935-G-C

Variant summary

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

The ENST00000611156.4(ABO):​c.793C>A​(p.Leu265Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 1,611,770 control chromosomes in the GnomAD database, including 9,539 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (1266 hom., cov: 32)
  • Exomes 𝑓: 0.089 (8273 hom.)
• Consequence: ABO ENST00000611156.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.11
• Publications: 280 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=0.0041951835).
• 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.807C>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.793C>A	p.Leu265Met	missense	Exon 8 of 8	ENSP00000483265.1	A0A087X0C2
	ABO	ENST00000453660.4	TSL:1	n.825C>A		non_coding_transcript_exon	Exon 7 of 7
	ABO	ENST00000538324.2	TSL:5	c.793C>A	p.Leu265Met	missense	Exon 8 of 9	ENSP00000483018.1	A0A087X009

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17434 AN: 151750 Hom.: 1264 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.118 AC: 28536 AN: 242686 AF XY: 0.125

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.0551

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.182

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.0774

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0894 AC: 130539 AN: 1459902 Hom.: 8273 Cov.: 74 AF XY: 0.0951 AC XY: 69095 AN XY: 726180

African (AFR) AF: 0.166 AC: 5529 AN: 33388

American (AMR) AF: 0.0555 AC: 2466 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3252 AN: 26066

East Asian (EAS) AF: 0.179 AC: 7111 AN: 39616

South Asian (SAS) AF: 0.259 AC: 22309 AN: 86022

European-Finnish (FIN) AF: 0.136 AC: 7220 AN: 53144

Middle Eastern (MID) AF: 0.149 AC: 862 AN: 5766

European-Non Finnish (NFE) AF: 0.0680 AC: 75598 AN: 1111176

Other (OTH) AF: 0.103 AC: 6192 AN: 60312

GnomAD4 genome AF: 0.115 AC: 17447 AN: 151868 Hom.: 1266 Cov.: 32 AF XY: 0.119 AC XY: 8817 AN XY: 74234

African (AFR) AF: 0.158 AC: 6542 AN: 41336

American (AMR) AF: 0.0738 AC: 1127 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3470

East Asian (EAS) AF: 0.180 AC: 926 AN: 5140

South Asian (SAS) AF: 0.256 AC: 1230 AN: 4804

European-Finnish (FIN) AF: 0.136 AC: 1438 AN: 10580

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0795 AC: 5403 AN: 67940

Other (OTH) AF: 0.104 AC: 220 AN: 2112

Alfa AF: 0.0911 Hom.: 2933

Bravo AF: 0.106

TwinsUK AF: 0.0618 AC: 229

ALSPAC AF: 0.0579 AC: 223

ESP6500AA AF: 0.159 AC: 617

ESP6500EA AF: 0.0741 AC: 611

ExAC AF: 0.118 AC: 14304

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	0.0010
DANN	Benign	0.46
DEOGEN2	Benign	0.0025	T
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0042	T
PhyloP100		-4.1
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.24	T
Vest4		0.075
GERP RS		-8.8
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
gMVP		0.090

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: rs8176746; hg19: chr9-136131322; COSMIC: COSV107533855;