9-133255928-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G267R) has been classified 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 no assertion criteria provided B:1
• Conservation: PhyloP100: -0.517

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

Verdict is Benign. Variant got -13 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 id is 242740.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-133255928-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.800G>C	p.Gly267Ala	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.800G>C	p.Gly267Ala	missense_variant	8/9	5		A2

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

GnomAD3 exomes AF: 0.118 AC: 28678 AN: 243428 Hom.: 2310 AF XY: 0.125 AC XY: 16600 AN XY: 132554

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 SAS exome AF: 0.260

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

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0556

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.0681

Gnomad4 OTH exome AF: 0.103

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

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0737

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.103

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Three Vessel Coronary Disease Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T
MetaRNN	Benign	0.0049	T;T
PrimateAI	Benign	0.43	T
Sift4G	Benign	1.0	T;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

Publications

LitVar

Other links and lift over

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