rs2073824

Positions:

• chr9-133257246-A-G

Variant summary

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

The ENST00000538324.2(ABO):​c.371+163T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,498 control chromosomes in the GnomAD database, including 12,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (12628 hom., cov: 31)
• Consequence: ABO ENST00000538324.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.29

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 (BayesDel_noAF=-0.96).
• BP6: Variant 9-133257246-A-G is Benign according to our data. Variant chr9-133257246-A-G is described in ClinVar as [Benign]. Clinvar id is 812631.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-133257246-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.371+163T>C		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.371+163T>C		intron_variant		5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60593 AN: 151380 Hom.: 12606 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.379

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.400 AC: 60652 AN: 151498 Hom.: 12628 Cov.: 31 AF XY: 0.404 AC XY: 29888 AN XY: 74010

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.376

Alfa AF: 0.352 Hom.: 9374

Bravo AF: 0.413

Asia WGS AF: 0.505 AC: 1753 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Three Vessel Coronary Disease Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.20
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		2.0

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: rs2073824; hg19: chr9-136132633; COSMIC: COSV71743520;