chr1-24927826-C-A

Variant names:

• chr1-24927826-C-A
• rs7517302
• NM_004350.3:c.283-96G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004350.3(RUNX3):​c.283-96G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RUNX3 NM_004350.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 23 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_004350.3	c.283-96G>T		intron_variant	Intron 1 of 4	ENST00000308873.11	NP_004341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000308873.11	c.283-96G>T		intron_variant	Intron 1 of 4	1	NM_004350.3	ENSP00000308051.6
RUNX3	ENST00000338888.4	c.325-96G>T		intron_variant	Intron 3 of 6	1		ENSP00000343477.3
RUNX3	ENST00000399916.5	c.325-96G>T		intron_variant	Intron 2 of 5	2		ENSP00000382800.1
RUNX3	ENST00000496967.1	n.57-96G>T		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 912264 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 469266

African (AFR) AF: 0.00 AC: 0 AN: 23040

American (AMR) AF: 0.00 AC: 0 AN: 41266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20692

East Asian (EAS) AF: 0.00 AC: 0 AN: 36788

South Asian (SAS) AF: 0.00 AC: 0 AN: 70498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4564

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 623854

Other (OTH) AF: 0.00 AC: 0 AN: 41838

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.59
DANN	Benign	0.60
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs7517302; hg19: chr1-25254317;