Variant chr1-24927826-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004350.3(RUNX3):c.283-96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,062,078 control chromosomes in the GnomAD database, including 166,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.53 ( 21523 hom., cov: 32)

Exomes 𝑓: 0.56 ( 145048 hom. )

Consequence

RUNX3
NM_004350.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.67

Variant links:

Genes affected

RUNX3 (HGNC:10473): (RUNX family transcription factor 3) This gene encodes a member of the runt domain-containing family of transcription factors. A heterodimer of this protein and a beta subunit forms a complex that binds to the core DNA sequence 5'-PYGPYGGT-3' found in a number of enhancers and promoters, and can either activate or suppress transcription. It also interacts with other transcription factors. It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

RUNX3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-24927826-C-T is Benign according to our data. Variant chr1-24927826-C-T is described in ClinVar as [Benign]. Clinvar id is 2688389.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX3	NM_004350.3 linkuse as main transcript	c.283-96G>A		intron_variant		ENST00000308873.11

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
RUNX3	ENST00000308873.11 linkuse as main transcript	c.283-96G>A	intron_variant	1	NM_004350.3		Q13761-1
RUNX3	ENST00000338888.4 linkuse as main transcript	c.325-96G>A	intron_variant	1		P1	Q13761-2
RUNX3	ENST00000399916.5 linkuse as main transcript	c.325-96G>A	intron_variant	2		P1	Q13761-2
RUNX3	ENST00000496967.1 linkuse as main transcript	n.57-96G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80426

AN:

151894

Hom.:

21481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.708

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.538

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.525

GnomAD4 exome

AF:

0.562

AC:

511551

AN:

910066

Hom.:

145048

AF XY:

0.562

AC XY:

262980

AN XY:

468180

show subpopulations

Gnomad4 AFR exome

AF:

0.457

Gnomad4 AMR exome

AF:

0.631

Gnomad4 ASJ exome

AF:

0.526

Gnomad4 EAS exome

AF:

0.547

Gnomad4 SAS exome

AF:

0.574

Gnomad4 FIN exome

AF:

0.554

Gnomad4 NFE exome

AF:

0.564

Gnomad4 OTH exome

AF:

0.553

GnomAD4 genome

AF:

0.530

AC:

80523

AN:

152012

Hom.:

21523

Cov.:

AF XY:

0.528

AC XY:

39232

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.458

Gnomad4 AMR

AF:

0.558

Gnomad4 ASJ

AF:

0.538

Gnomad4 EAS

AF:

0.518

Gnomad4 SAS

AF:

0.576

Gnomad4 FIN

AF:

0.565

Gnomad4 NFE

AF:

0.557

Gnomad4 OTH

AF:

0.520

Alfa

AF:

0.551

Hom.:

12414

Bravo

AF:

0.534

Asia WGS

AF:

0.505

AC:

1752

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 54. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.75

DANN

Benign

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over