rs1053878

Positions:

• chr9-133256264-G-A

Variant summary

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

The ENST00000538324.2(ABO):​c.464C>T​(p.Pro155Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 1,613,020 control chromosomes in the GnomAD database, including 6,955 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 (1487 hom., cov: 34)
  • Exomes 𝑓: 0.076 (5468 hom.)
• Consequence: ABO ENST00000538324.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27

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=0.002676636).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.464C>T	p.Pro155Leu	missense_variant	8/8		NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.464C>T	p.Pro155Leu	missense_variant	8/9	5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17639 AN: 152088 Hom.: 1484 Cov.: 34

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.0834 AC: 20310 AN: 243522 Hom.: 1276 AF XY: 0.0801 AC XY: 10665 AN XY: 133164

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.0383

Gnomad ASJ exome AF: 0.0913

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.0338

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.0714

Gnomad OTH exome AF: 0.0746

GnomAD4 exome AF: 0.0758 AC: 110783 AN: 1460814 Hom.: 5468 Cov.: 77 AF XY: 0.0739 AC XY: 53732 AN XY: 726686

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.0418

Gnomad4 ASJ exome AF: 0.0850

Gnomad4 EAS exome AF: 0.210

Gnomad4 SAS exome AF: 0.0336

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0691

Gnomad4 OTH exome AF: 0.0816

GnomAD4 genome AF: 0.116 AC: 17662 AN: 152206 Hom.: 1487 Cov.: 34 AF XY: 0.117 AC XY: 8699 AN XY: 74416

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.0418

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.0679

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0794 Hom.: 1074

Bravo AF: 0.118

TwinsUK AF: 0.0696 AC: 258

ALSPAC AF: 0.0727 AC: 280

ESP6500AA AF: 0.210 AC: 818

ESP6500EA AF: 0.0692 AC: 571

ExAC AF: 0.0867 AC: 10457

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Benign	0.66
DEOGEN2	Benign	0.13	T;.
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.77	T;T
MetaRNN	Benign	0.0027	T;T
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.079	T;T
Vest4		0.16
GERP RS		3.8
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.2
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1053878; hg19: chr9-136131651; COSMIC: COSV71743421;