ENST00000538324.2:c.800G>C

Variant names:

• chr9-133255928-C-G
• rs8176747
• ENST00000611156.4:c.800G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000538324.2(ABO):​c.800G>C​(p.Gly267Ala) 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 1,612,132 control chromosomes in the GnomAD database, including 9,548 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1265 hom., cov: 32)
  • Exomes 𝑓: 0.089 (8283 hom.)
• Consequence: ABO ENST00000538324.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.517
• Publications: 139 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048752427).
• BP6: Variant 9-133255928-C-G is Benign according to our data. Variant chr9-133255928-C-G is described in ClinVar as Benign. ClinVar VariationId is 242740.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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: ENST00000538324.2. 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.814G>C		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.800G>C	p.Gly267Ala	missense	Exon 8 of 8	ENSP00000483265.1	A0A087X0C2
	ABO	ENST00000453660.4	TSL:1	n.832G>C		non_coding_transcript_exon	Exon 7 of 7
	ABO	ENST00000538324.2	TSL:5	c.800G>C	p.Gly267Ala	missense	Exon 8 of 9	ENSP00000483018.1	A0A087X009

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17433 AN: 151762 Hom.: 1263 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0801

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.118 AC: 28678 AN: 243428 AF XY: 0.125

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.0552

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.182

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.0777

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0895 AC: 130626 AN: 1460250 Hom.: 8283 Cov.: 74 AF XY: 0.0952 AC XY: 69147 AN XY: 726344

African (AFR) AF: 0.166 AC: 5533 AN: 33422

American (AMR) AF: 0.0556 AC: 2475 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3253 AN: 26078

East Asian (EAS) AF: 0.180 AC: 7118 AN: 39644

South Asian (SAS) AF: 0.259 AC: 22334 AN: 86082

European-Finnish (FIN) AF: 0.136 AC: 7228 AN: 53196

Middle Eastern (MID) AF: 0.150 AC: 863 AN: 5768

European-Non Finnish (NFE) AF: 0.0681 AC: 75629 AN: 1111230

Other (OTH) AF: 0.103 AC: 6193 AN: 60314

GnomAD4 genome AF: 0.115 AC: 17446 AN: 151882 Hom.: 1265 Cov.: 32 AF XY: 0.119 AC XY: 8821 AN XY: 74246

African (AFR) AF: 0.158 AC: 6536 AN: 41350

American (AMR) AF: 0.0737 AC: 1127 AN: 15288

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

East Asian (EAS) AF: 0.181 AC: 932 AN: 5138

South Asian (SAS) AF: 0.256 AC: 1229 AN: 4806

European-Finnish (FIN) AF: 0.136 AC: 1438 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0796 AC: 5405 AN: 67930

Other (OTH) AF: 0.103 AC: 218 AN: 2108

Alfa AF: 0.0955 Hom.: 296

Bravo AF: 0.106

TwinsUK AF: 0.0615 AC: 228

ALSPAC AF: 0.0576 AC: 222

ESP6500AA AF: 0.154 AC: 605

ESP6500EA AF: 0.0736 AC: 608

ExAC AF: 0.118 AC: 14311

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Three Vessel Coronary Disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	0.0020
DANN	Benign	0.40
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0049	T
PhyloP100		-0.52
PrimateAI	Benign	0.43	T
Sift4G	Benign	1.0	T
Vest4		0.055
GERP RS		-8.4
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
gMVP		0.24

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: rs8176747; hg19: chr9-136131315; COSMIC: COSV71743586;