ENST00000538324.2:c.793C>A

Variant names:

• chr9-133255935-G-T
• rs8176746
• ENST00000538324.2:c.793C>A

Variant summary

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

The ENST00000538324.2(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. 7/10 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 0.11 (1266 hom., cov: 32)
  • Exomes 𝑓: 0.089 (8273 hom.)
• Consequence: ABO ENST00000538324.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.11

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=0.0041951835).
• 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 rank	MANE	Protein	UniProt
ABO	NM_020469.3	c.793C>A	p.Leu265Met	missense_variant	Exon 8 of 8		NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.793C>A	p.Leu265Met	missense_variant	Exon 8 of 9	5		ENSP00000483018.1

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

GnomAD3 exomes AF: 0.118 AC: 28536 AN: 242686 Hom.: 2297 AF XY: 0.125 AC XY: 16540 AN XY: 132250

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 SAS exome AF: 0.259

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

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0555

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.0680

Gnomad4 OTH exome AF: 0.103

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

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0738

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.0795

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0862 Hom.: 1826

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 v4.3

Name	Calibrated prediction	Score	Prediction
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;T
MetaRNN	Benign	0.0042	T;T
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.24	T;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

Publications

LitVar

Other links and lift over

dbSNP: rs8176746; hg19: chr9-136131322;