rs6688058

Positions:

• chr1-24948507-G-A

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX3-AS1	NR_183339.1	n.1731-8905G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000338888.4	c.58+16007C>T		intron_variant		1		ENSP00000343477	P1
RUNX3	ENST00000479341.1	n.168+16007C>T		intron_variant, non_coding_transcript_variant		1
RUNX3	ENST00000399916.5	c.58+16007C>T		intron_variant		2		ENSP00000382800	P1

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

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0558

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.130

Alfa AF: 0.131 Hom.: 501

Bravo AF: 0.137

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6688058; hg19: chr1-25274998;