rs4648884

Variant names:

• chr1-24934895-T-C
• rs4648884
• ENST00000338888.4:c.59-5043A>G

Variant summary

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

The NM_001031680.2(RUNX3):​c.59-5043A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,918 control chromosomes in the GnomAD database, including 21,523 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 0.53 (21523 hom., cov: 31)
• Consequence: RUNX3 NM_001031680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 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_001031680.2		c.59-5043A>G		intron	N/A	NP_001026850.1	Q13761-2
	RUNX3	NM_001320672.1		c.59-5043A>G		intron	N/A	NP_001307601.1	Q13761-2
	RUNX3-AS1	NR_183339.1		n.1570+2869T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000338888.4	TSL:1	c.59-5043A>G		intron	N/A	ENSP00000343477.3	Q13761-2
	RUNX3	ENST00000479341.1	TSL:1	n.169-5043A>G		intron	N/A
	RUNX3	ENST00000399916.5	TSL:2	c.59-5043A>G		intron	N/A	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80297 AN: 151800 Hom.: 21489 Cov.: 31

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.529 AC: 80376 AN: 151918 Hom.: 21523 Cov.: 31 AF XY: 0.528 AC XY: 39196 AN XY: 74252

African (AFR) AF: 0.451 AC: 18681 AN: 41398

American (AMR) AF: 0.555 AC: 8473 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1875 AN: 3470

East Asian (EAS) AF: 0.517 AC: 2666 AN: 5152

South Asian (SAS) AF: 0.589 AC: 2830 AN: 4806

European-Finnish (FIN) AF: 0.567 AC: 5980 AN: 10544

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37989 AN: 67960

Other (OTH) AF: 0.519 AC: 1095 AN: 2110

Alfa AF: 0.544 Hom.: 3976

Bravo AF: 0.533

Asia WGS AF: 0.505 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.72
PhyloP100		-0.18
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: rs4648884; hg19: chr1-25261386;