rs2073824

Variant names:

• chr9-133257246-A-G
• rs2073824
• ENST00000611156.4:c.371+163T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000611156.4(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 ENST00000611156.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.29
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 812631.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.385+163T>C		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.371+163T>C		intron_variant	Intron 7 of 7	5		ENSP00000483265.1

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

African (AFR) AF: 0.461 AC: 18978 AN: 41126

American (AMR) AF: 0.477 AC: 7276 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1442 AN: 3466

East Asian (EAS) AF: 0.531 AC: 2719 AN: 5118

South Asian (SAS) AF: 0.485 AC: 2339 AN: 4818

European-Finnish (FIN) AF: 0.335 AC: 3533 AN: 10542

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23264 AN: 67870

Other (OTH) AF: 0.376 AC: 793 AN: 2108

Alfa AF: 0.361 Hom.: 13075

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

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.20
PhyloP100		-1.3
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

Other links and lift over

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