9-133256205-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000538324.2(ABO):c.523C>G(p.Arg175Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,612,732 control chromosomes in the GnomAD database, including 12,420 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 no classification for the single variant (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R175H) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.13 (1551 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10869 hom.)
• Consequence: ABO ENST00000538324.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005328357).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.523C>G	p.Arg175Gly	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.523C>G	p.Arg175Gly	missense_variant	8/9	5		A2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19843 AN: 152054 Hom.: 1549 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.132 AC: 32364 AN: 244556 Hom.: 2764 AF XY: 0.140 AC XY: 18630 AN XY: 133514

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.0663

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.182

Gnomad SAS exome AF: 0.267

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.0987

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.109 AC: 159318 AN: 1460558 Hom.: 10869 Cov.: 81 AF XY: 0.114 AC XY: 83059 AN XY: 726598

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.0677

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.0905

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.130 AC: 19857 AN: 152174 Hom.: 1551 Cov.: 33 AF XY: 0.134 AC XY: 9975 AN XY: 74404

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0915

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0887 Hom.: 170

Bravo AF: 0.121

TwinsUK AF: 0.0879 AC: 326

ALSPAC AF: 0.0791 AC: 305

ESP6500AA AF: 0.155 AC: 644

ESP6500EA AF: 0.0910 AC: 765

ExAC AF: 0.134 AC: 16131

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	9.7
Dann	Benign	0.46
DEOGEN2	Benign	0.063	T;.
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.52	T;T
MetaRNN	Benign	0.0053	T;T
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.29	T;T
Vest4		0.048
GERP RS		-1.1
gMVP		0.64

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: rs7853989; hg19: chr9-136131592; COSMIC: COSV71743505;