9-133268647-A-T

Position:

• chr9-133268647-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000538324.2(ABO):​c.29-6479T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,090 control chromosomes in the GnomAD database, including 8,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.34 (8935 hom., cov: 32)
• Consequence: ABO ENST00000538324.2 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.196

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-133268647-A-T is Benign according to our data. Variant chr9-133268647-A-T is described in ClinVar as [Benign]. Clinvar id is 812628.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.29-6479T>A		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.29-6479T>A		intron_variant		5		ENSP00000483018	A2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51234 AN: 151972 Hom.: 8923 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.337 AC: 51273 AN: 152090 Hom.: 8935 Cov.: 32 AF XY: 0.336 AC XY: 24987 AN XY: 74342

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.366

Alfa AF: 0.234 Hom.: 530

Bravo AF: 0.332

Asia WGS AF: 0.331 AC: 1153 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.27

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: rs8176668; hg19: chr9-136144059; COSMIC: COSV71743476;