chr1-24948507-G-A

Variant names:

• chr1-24948507-G-A
• rs6688058
• ENST00000338888.4:c.58+16007C>T

Variant summary

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

The ENST00000338888.4(RUNX3):​c.58+16007C>T variant causes a intron change. The variant allele was found at a frequency of 0.136 in 152,122 control chromosomes in the GnomAD database, including 1,476 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 0.14 (1476 hom., cov: 32)
• Consequence: RUNX3 ENST00000338888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.22
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.167 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+16007C>T		intron	N/A	NP_001026850.1
	RUNX3	NM_001320672.1		c.58+16007C>T		intron	N/A	NP_001307601.1
	RUNX3-AS1	NR_183339.1		n.1731-8905G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000338888.4	TSL:1	c.58+16007C>T		intron	N/A	ENSP00000343477.3
	RUNX3	ENST00000479341.1	TSL:1	n.168+16007C>T		intron	N/A
	RUNX3	ENST00000399916.5	TSL:2	c.58+16007C>T		intron	N/A	ENSP00000382800.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20686 AN: 152004 Hom.: 1477 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0559

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.136 AC: 20684 AN: 152122 Hom.: 1476 Cov.: 32 AF XY: 0.135 AC XY: 10065 AN XY: 74372

African (AFR) AF: 0.153 AC: 6351 AN: 41490

American (AMR) AF: 0.134 AC: 2054 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3468

East Asian (EAS) AF: 0.0558 AC: 289 AN: 5178

South Asian (SAS) AF: 0.177 AC: 850 AN: 4810

European-Finnish (FIN) AF: 0.133 AC: 1412 AN: 10596

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.128 AC: 8728 AN: 67974

Other (OTH) AF: 0.130 AC: 274 AN: 2104

Alfa AF: 0.132 Hom.: 1035

Bravo AF: 0.137

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.31
PhyloP100		4.2
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: rs6688058; hg19: chr1-25274998;