1-24938167-C-G

Position:

• chr1-24938167-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031680.2(RUNX3):​c.59-8315G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,156 control chromosomes in the GnomAD database, including 43,924 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (43924 hom., cov: 32)
• Consequence: RUNX3 NM_001031680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX3	NM_001031680.2	c.59-8315G>C		intron_variant			NP_001026850.1
RUNX3	NM_001320672.1	c.59-8315G>C		intron_variant			NP_001307601.1
RUNX3	XM_005246024.5	c.59-8315G>C		intron_variant			XP_005246081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000338888.4	c.59-8315G>C		intron_variant		1		ENSP00000343477.3
RUNX3	ENST00000479341.1	n.169-8315G>C		intron_variant		1
RUNX3	ENST00000399916.5	c.59-8315G>C		intron_variant		2		ENSP00000382800.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115288 AN: 152038 Hom.: 43898 Cov.: 32

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.758 AC: 115355 AN: 152156 Hom.: 43924 Cov.: 32 AF XY: 0.754 AC XY: 56110 AN XY: 74382

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.759

Alfa AF: 0.750 Hom.: 5344

Bravo AF: 0.767

Asia WGS AF: 0.764 AC: 2656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs906296; hg19: chr1-25264658;