rs512770

Positions:

• chr9-133258116-G-A
• chr9-133258116-G-C
• chr9-133258116-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000538324.2(ABO):​c.220C>T​(p.Pro74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,613,350 control chromosomes in the GnomAD database, including 41,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4739 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36790 hom.)
• Consequence: ABO ENST00000538324.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.22

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024269521).
• BP6: Variant 9-133258116-G-A is Benign according to our data. Variant chr9-133258116-G-A is described in ClinVar as [Benign]. Clinvar id is 769757.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.220C>T	p.Pro74Ser	missense_variant	5/8		NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.220C>T	p.Pro74Ser	missense_variant	5/9	5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36421 AN: 151908 Hom.: 4732 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.216 AC: 316290 AN: 1461324 Hom.: 36790 Cov.: 32 AF XY: 0.214 AC XY: 155817 AN XY: 726962

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.470

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.240 AC: 36446 AN: 152026 Hom.: 4739 Cov.: 32 AF XY: 0.240 AC XY: 17827 AN XY: 74326

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.232

Alfa AF: 0.218 Hom.: 9342

Bravo AF: 0.261

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	20
DEOGEN2	Benign	0.10	T;.
LIST_S2	Benign	0.70	T;T
MetaRNN	Benign	0.0024	T;T
Sift4G	Benign	0.068	T;T
Vest4		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs512770; hg19: -;