rs2236852

Positions:

• chr1-24917276-A-G
• chr1-24917276-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004350.3(RUNX3):​c.544+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_004350.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX3	NM_004350.3	c.544+1964T>C		intron_variant		ENST00000308873.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX3	ENST00000308873.11	c.544+1964T>C		intron_variant		1	NM_004350.3
RUNX3	ENST00000338888.4	c.586+1964T>C		intron_variant		1		P1
RUNX3	ENST00000399916.5	c.586+1964T>C		intron_variant		2		P1
RUNX3	ENST00000496967.1	n.318+1964T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.454

Alfa AF: 0.435 Hom.: 26467

Bravo AF: 0.469

Asia WGS AF: 0.568 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.69

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