1-24952689-C-T

Position:

• chr1-24952689-C-T

Variant summary

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

The NM_001031680.2(RUNX3):​c.58+11825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,020 control chromosomes in the GnomAD database, including 22,129 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 0.54 (22129 hom., cov: 32)
• Consequence: RUNX3 NM_001031680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX3	NM_001031680.2	c.58+11825G>A		intron_variant			NP_001026850.1
RUNX3	NM_001320672.1	c.58+11825G>A		intron_variant			NP_001307601.1
RUNX3	XM_005246024.5	c.58+11825G>A		intron_variant			XP_005246081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000338888.4	c.58+11825G>A		intron_variant		1		ENSP00000343477.3
RUNX3	ENST00000479341.1	n.168+11825G>A		intron_variant		1
RUNX3	ENST00000399916.5	c.58+11825G>A		intron_variant		2		ENSP00000382800.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81789 AN: 151902 Hom.: 22095 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.539 AC: 81872 AN: 152020 Hom.: 22129 Cov.: 32 AF XY: 0.546 AC XY: 40557 AN XY: 74314

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.541

Alfa AF: 0.513 Hom.: 18331

Bravo AF: 0.539

Asia WGS AF: 0.640 AC: 2228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2135756; hg19: chr1-25279180;