9-133256028-C-T

Variant summary

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

The ENST00000538324.2(ABO):c.700G>A(p.Gly234Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,584,348 control chromosomes in the GnomAD database, including 9,335 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).

• Frequency:
  • Genomes: 𝑓 0.12 (1298 hom., cov: 32)
  • Exomes 𝑓: 0.089 (8037 hom.)
• Consequence: ABO ENST00000538324.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.461

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=0.0038890243).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.700G>A	p.Gly234Ser	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.700G>A	p.Gly234Ser	missense_variant	8/9	5		A2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17487 AN: 151862 Hom.: 1296 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0540

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.106

GnomAD3 exomes AF: 0.119 AC: 23681 AN: 199484 Hom.: 1988 AF XY: 0.127 AC XY: 13722 AN XY: 108416

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.0567

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.183

Gnomad SAS exome AF: 0.260

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.0765

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0888 AC: 127257 AN: 1432368 Hom.: 8037 Cov.: 79 AF XY: 0.0945 AC XY: 67092 AN XY: 710326

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.0565

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.0677

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.115 AC: 17501 AN: 151980 Hom.: 1298 Cov.: 32 AF XY: 0.119 AC XY: 8864 AN XY: 74306

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0743

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0833 Hom.: 852

Bravo AF: 0.106

TwinsUK AF: 0.0639 AC: 237

ALSPAC AF: 0.0586 AC: 226

ESP6500AA AF: 0.157 AC: 647

ESP6500EA AF: 0.0722 AC: 603

ExAC AF: 0.103 AC: 12294

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.18
Cadd	Benign	7.6
Dann	Benign	0.62
DEOGEN2	Benign	0.12	T;.
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.14	T;T
MetaRNN	Benign	0.0039	T;T
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.24	T;T
Vest4		0.046
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.55

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: rs8176743; hg19: chr9-136131415; COSMIC: COSV71743503;