rs2236850

Variant names:

• chr1-24913850-T-A
• rs2236850
• NM_004350.3:c.544+5390A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-24913850-T-A
• chr1-24913850-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004350.3(RUNX3):​c.544+5390A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: RUNX3 NM_004350.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 11 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004350.3. 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_004350.3	MANE Select	c.544+5390A>T		intron	N/A	NP_004341.1	Q13761-1
	RUNX3	NM_001031680.2		c.586+5390A>T		intron	N/A	NP_001026850.1	Q13761-2
	RUNX3	NM_001320672.1		c.586+5390A>T		intron	N/A	NP_001307601.1	Q13761-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000308873.11	TSL:1 MANE Select	c.544+5390A>T		intron	N/A	ENSP00000308051.6	Q13761-1
	RUNX3	ENST00000338888.4	TSL:1	c.586+5390A>T		intron	N/A	ENSP00000343477.3	Q13761-2
	RUNX3	ENST00000399916.5	TSL:2	c.586+5390A>T		intron	N/A	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.82
PhyloP100		0.047

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2236850;

hg19: chr1-25240341;