1-24927826-C-T

Variant summary

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

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67

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]

ACMG classification

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	c.283-96G>A		intron_variant		ENST00000308873.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX3	ENST00000308873.11	c.283-96G>A		intron_variant		1	NM_004350.3
RUNX3	ENST00000338888.4	c.325-96G>A		intron_variant		1		P1
RUNX3	ENST00000399916.5	c.325-96G>A		intron_variant		2		P1
RUNX3	ENST00000496967.1	n.57-96G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80426 AN: 151894 Hom.: 21481 Cov.: 32

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

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.: 32 AF XY: 0.528 AC XY: 39232 AN XY: 74282

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

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

Other links and lift over

dbSNP: rs7517302; hg19: chr1-25254317; COSMIC: COSV58243002; COSMIC: COSV58243002;