chr1-24952689-C-T

Variant names:

• chr1-24952689-C-T
• rs2135756
• ENST00000338888.4:c.58+11825G>A

Variant summary

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

The ENST00000338888.4(RUNX3):​c.58+11825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,020 control chromosomes in the GnomAD database, including 22,129 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 0.54 (22129 hom., cov: 32)
• Consequence: RUNX3 ENST00000338888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 9 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000338888.4. 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_001031680.2		c.58+11825G>A		intron	N/A	NP_001026850.1
	RUNX3	NM_001320672.1		c.58+11825G>A		intron	N/A	NP_001307601.1
	RUNX3-AS1	NR_183339.1		n.1731-4723C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000338888.4	TSL:1	c.58+11825G>A		intron	N/A	ENSP00000343477.3
	RUNX3	ENST00000479341.1	TSL:1	n.168+11825G>A		intron	N/A
	RUNX3	ENST00000399916.5	TSL:2	c.58+11825G>A		intron	N/A	ENSP00000382800.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81789 AN: 151902 Hom.: 22095 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.539 AC: 81872 AN: 152020 Hom.: 22129 Cov.: 32 AF XY: 0.546 AC XY: 40557 AN XY: 74314

African (AFR) AF: 0.541 AC: 22400 AN: 41412

American (AMR) AF: 0.606 AC: 9266 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1571 AN: 3472

East Asian (EAS) AF: 0.644 AC: 3329 AN: 5172

South Asian (SAS) AF: 0.550 AC: 2652 AN: 4820

European-Finnish (FIN) AF: 0.599 AC: 6348 AN: 10590

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34441 AN: 67950

Other (OTH) AF: 0.541 AC: 1144 AN: 2114

Alfa AF: 0.516 Hom.: 24606

Bravo AF: 0.539

Asia WGS AF: 0.640 AC: 2228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.54
PhyloP100		2.2
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: rs2135756; hg19: chr1-25279180;