rs742230

chr1-24924933-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX3	NM_004350.3	c.439+2641C>T		intron_variant		ENST00000308873.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX3	ENST00000308873.11	c.439+2641C>T		intron_variant		1	NM_004350.3
RUNX3	ENST00000338888.4	c.481+2641C>T		intron_variant		1		P1
RUNX3	ENST00000399916.5	c.481+2641C>T		intron_variant		2		P1
RUNX3	ENST00000496967.1	n.213+2641C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.519

Alfa AF: 0.559 Hom.: 29646

Bravo AF: 0.536

Asia WGS AF: 0.508 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.37
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs742230; hg19: chr1-25251424;