9-133256963-T-C

Variant summary

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

The NM_020469.3(ABO):c.371+446A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,922 control chromosomes in the GnomAD database, including 12,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency: Genomes: 𝑓 0.40 (12498 hom., cov: 32)
• Consequence: ABO NM_020469.3 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.387

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=-0.91).
• BP6: Variant 9-133256963-T-C is Benign according to our data. Variant chr9-133256963-T-C is described in ClinVar as [Benign]. Clinvar id is 812630.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.371+446A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.371+446A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60336 AN: 151804 Hom.: 12475 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.398 AC: 60394 AN: 151922 Hom.: 12498 Cov.: 32 AF XY: 0.401 AC XY: 29753 AN XY: 74266

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.374

Alfa AF: 0.388 Hom.: 1731

Bravo AF: 0.409

Asia WGS AF: 0.473 AC: 1643 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	-0.91
Cadd	Benign	2.8
Dann	Benign	0.65
RBP_binding_hub_radar		0.77
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: rs8176731; hg19: chr9-136132350; COSMIC: COSV71743598;