1-24902248-G-A

Variant names:

• chr1-24902248-G-A
• rs573389125
• NM_004350.3:c.1122C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004350.3(RUNX3):​c.1122C>T​(p.Gly374Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000587 in 1,582,372 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (19 hom.)
• Consequence: RUNX3 NM_004350.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02
• Publications: 0 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 1-24902248-G-A is Benign according to our data. Variant chr1-24902248-G-A is described in ClinVar as Benign. ClinVar VariationId is 795881.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BS2: High AC in GnomAd4 at 48 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004350.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	NM_004350.3	MANE Select	c.1122C>T	p.Gly374Gly	synonymous	Exon 5 of 5	NP_004341.1	Q13761-1
	RUNX3	NM_001031680.2		c.1164C>T	p.Gly388Gly	synonymous	Exon 6 of 6	NP_001026850.1	Q13761-2
	RUNX3	NM_001320672.1		c.1164C>T	p.Gly388Gly	synonymous	Exon 7 of 7	NP_001307601.1	Q13761-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX3	ENST00000308873.11	TSL:1 MANE Select	c.1122C>T	p.Gly374Gly	synonymous	Exon 5 of 5	ENSP00000308051.6	Q13761-1
	RUNX3	ENST00000338888.4	TSL:1	c.1164C>T	p.Gly388Gly	synonymous	Exon 7 of 7	ENSP00000343477.3	Q13761-2
	RUNX3	ENST00000399916.5	TSL:2	c.1164C>T	p.Gly388Gly	synonymous	Exon 6 of 6	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152244 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00137 AC: 267 AN: 194218 AF XY: 0.00180

Gnomad AFR exome AF: 0.0000858

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000595

Gnomad OTH exome AF: 0.000597

GnomAD4 exome AF: 0.000616 AC: 881 AN: 1430010 Hom.: 19 Cov.: 31 AF XY: 0.000905 AC XY: 641 AN XY: 708344

African (AFR) AF: 0.0000601 AC: 2 AN: 33256

American (AMR) AF: 0.00 AC: 0 AN: 38510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25448

East Asian (EAS) AF: 0.00 AC: 0 AN: 38740

South Asian (SAS) AF: 0.00964 AC: 793 AN: 82262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49182

Middle Eastern (MID) AF: 0.00348 AC: 17 AN: 4890

European-Non Finnish (NFE) AF: 0.0000255 AC: 28 AN: 1098402

Other (OTH) AF: 0.000691 AC: 41 AN: 59320

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152362 Hom.: 1 Cov.: 32 AF XY: 0.000416 AC XY: 31 AN XY: 74512

African (AFR) AF: 0.0000240 AC: 1 AN: 41580

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00807 AC: 39 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000171 Hom.: 0

Bravo AF: 0.0000642

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.0
DANN	Benign	0.96
PhyloP100		1.0
Mutation Taster		=99/1	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: rs573389125; hg19: chr1-25228739;