1-24917276-A-G

Variant names:

• chr1-24917276-A-G
• rs2236852
• NM_004350.3:c.544+1964T>C

Variant summary

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

The NM_001031680.2(RUNX3):​c.586+1964T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,922 control chromosomes in the GnomAD database, including 16,050 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 0.46 (16050 hom., cov: 31)
• Consequence: RUNX3 NM_001031680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 12 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031680.2. 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+1964T>C		intron	N/A	NP_004341.1
	RUNX3	NM_001031680.2		c.586+1964T>C		intron	N/A	NP_001026850.1
	RUNX3	NM_001320672.1		c.586+1964T>C		intron	N/A	NP_001307601.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000308873.11	TSL:1 MANE Select	c.544+1964T>C		intron	N/A	ENSP00000308051.6
	RUNX3	ENST00000338888.4	TSL:1	c.586+1964T>C		intron	N/A	ENSP00000343477.3
	RUNX3	ENST00000399916.5	TSL:2	c.586+1964T>C		intron	N/A	ENSP00000382800.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69075 AN: 151802 Hom.: 16004 Cov.: 31

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.455 AC: 69173 AN: 151922 Hom.: 16050 Cov.: 31 AF XY: 0.455 AC XY: 33751 AN XY: 74254

African (AFR) AF: 0.498 AC: 20654 AN: 41434

American (AMR) AF: 0.487 AC: 7440 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1600 AN: 3470

East Asian (EAS) AF: 0.559 AC: 2887 AN: 5162

South Asian (SAS) AF: 0.585 AC: 2805 AN: 4798

European-Finnish (FIN) AF: 0.376 AC: 3969 AN: 10560

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28236 AN: 67910

Other (OTH) AF: 0.454 AC: 955 AN: 2104

Alfa AF: 0.437 Hom.: 57969

Bravo AF: 0.469

Asia WGS AF: 0.568 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.69
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236852; hg19: chr1-25243767; COSMIC: COSV58243050; COSMIC: COSV58243050;