rs742230

Variant names:

• chr1-24924933-G-A
• rs742230
• NM_004350.3:c.439+2641C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-24924933-G-A
• chr1-24924933-G-C
• chr1-24924933-G-T

Variant summary

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

The NM_004350.3(RUNX3):​c.439+2641C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,932 control chromosomes in the GnomAD database, including 21,590 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 (21590 hom., cov: 31)
• Consequence: RUNX3 NM_004350.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 17 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	NM_004350.3	MANE Select	c.439+2641C>T		intron	N/A	NP_004341.1
	RUNX3	NM_001031680.2		c.481+2641C>T		intron	N/A	NP_001026850.1
	RUNX3	NM_001320672.1		c.481+2641C>T		intron	N/A	NP_001307601.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000308873.11	TSL:1 MANE Select	c.439+2641C>T		intron	N/A	ENSP00000308051.6
	RUNX3	ENST00000338888.4	TSL:1	c.481+2641C>T		intron	N/A	ENSP00000343477.3
	RUNX3	ENST00000399916.5	TSL:2	c.481+2641C>T		intron	N/A	ENSP00000382800.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80562 AN: 151814 Hom.: 21549 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.531 AC: 80659 AN: 151932 Hom.: 21590 Cov.: 31 AF XY: 0.529 AC XY: 39302 AN XY: 74230

African (AFR) AF: 0.462 AC: 19142 AN: 41418

American (AMR) AF: 0.559 AC: 8543 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1868 AN: 3466

East Asian (EAS) AF: 0.508 AC: 2621 AN: 5158

South Asian (SAS) AF: 0.577 AC: 2777 AN: 4816

European-Finnish (FIN) AF: 0.566 AC: 5953 AN: 10518

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37870 AN: 67970

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

Alfa AF: 0.553 Hom.: 72691

Bravo AF: 0.536

Asia WGS AF: 0.508 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.37
DANN	Benign	0.54
PhyloP100		-1.4
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: rs742230; hg19: chr1-25251424;