1-24929953-G-A

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.-85C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,206,182 control chromosomes in the GnomAD database, including 186,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (17435 hom., cov: 32)
  • Exomes 𝑓: 0.56 (168604 hom.)
• Consequence: RUNX3 NM_004350.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0800

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=-0.74).
• BP6: Variant 1-24929953-G-A is Benign according to our data. Variant chr1-24929953-G-A is described in ClinVar as [Benign]. Clinvar id is 2688355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX3	NM_004350.3	c.-85C>T		5_prime_UTR_variant	1/5	ENST00000308873.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX3	ENST00000308873.11	c.-85C>T		5_prime_UTR_variant	1/5	1	NM_004350.3
RUNX3	ENST00000338888.4	c.59-101C>T		intron_variant		1		P1
RUNX3	ENST00000479341.1	n.169-101C>T		intron_variant, non_coding_transcript_variant		1
RUNX3	ENST00000399916.5	c.59-101C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 68588 AN: 150508 Hom.: 17420 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.562 AC: 592927 AN: 1055566 Hom.: 168604 Cov.: 37 AF XY: 0.562 AC XY: 280394 AN XY: 498516

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.586

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.539

GnomAD4 genome AF: 0.456 AC: 68626 AN: 150616 Hom.: 17435 Cov.: 32 AF XY: 0.457 AC XY: 33614 AN XY: 73584

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.471

Alfa AF: 0.484 Hom.: 2239

Bravo AF: 0.451

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 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 70. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	12
Dann	Uncertain	0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71514255; hg19: chr1-25256444;