ENST00000338888.4:c.59-8315G>C

Variant names:

• chr1-24938167-C-G
• rs906296
• ENST00000338888.4:c.59-8315G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000338888.4(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 ENST00000338888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 4 publications found

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-AS1 (HGNC:40513): (RUNX3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000338888.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	NM_001031680.2		c.59-8315G>C		intron	N/A	NP_001026850.1	Q13761-2
	RUNX3	NM_001320672.1		c.59-8315G>C		intron	N/A	NP_001307601.1	Q13761-2
	RUNX3-AS1	NR_183339.1		n.1571-575C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000338888.4	TSL:1	c.59-8315G>C		intron	N/A	ENSP00000343477.3	Q13761-2
	RUNX3	ENST00000479341.1	TSL:1	n.169-8315G>C		intron	N/A
	RUNX3	ENST00000399916.5	TSL:2	c.59-8315G>C		intron	N/A	ENSP00000382800.1	Q13761-2

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

African (AFR) AF: 0.741 AC: 30750 AN: 41486

American (AMR) AF: 0.794 AC: 12150 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2401 AN: 3470

East Asian (EAS) AF: 0.783 AC: 4052 AN: 5176

South Asian (SAS) AF: 0.790 AC: 3806 AN: 4818

European-Finnish (FIN) AF: 0.681 AC: 7215 AN: 10590

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52346 AN: 68000

Other (OTH) AF: 0.759 AC: 1604 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.53
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs906296; hg19: chr1-25264658;