chr1-24927713-G-A

Variant names:

• chr1-24927713-G-A
• rs114583699
• NM_004350.3:c.300C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_004350.3(RUNX3):​c.300C>T​(p.Asp100Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,613,950 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (14 hom.)
• Consequence: RUNX3 NM_004350.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.07
• Publications: 4 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-24927713-G-A is Benign according to our data. Variant chr1-24927713-G-A is described in ClinVar as Benign. ClinVar VariationId is 782679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00561 (854/152212) while in subpopulation AFR AF = 0.0191 (792/41526). AF 95% confidence interval is 0.018. There are 7 homozygotes in GnomAd4. There are 396 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 854 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.300C>T	p.Asp100Asp	synonymous	Exon 2 of 5	NP_004341.1	Q13761-1
	RUNX3	NM_001031680.2		c.342C>T	p.Asp114Asp	synonymous	Exon 3 of 6	NP_001026850.1	Q13761-2
	RUNX3	NM_001320672.1		c.342C>T	p.Asp114Asp	synonymous	Exon 4 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.300C>T	p.Asp100Asp	synonymous	Exon 2 of 5	ENSP00000308051.6	Q13761-1
	RUNX3	ENST00000338888.4	TSL:1	c.342C>T	p.Asp114Asp	synonymous	Exon 4 of 7	ENSP00000343477.3	Q13761-2
	RUNX3	ENST00000399916.5	TSL:2	c.342C>T	p.Asp114Asp	synonymous	Exon 3 of 6	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes AF: 0.00558 AC: 848 AN: 152094 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00143 AC: 359 AN: 251130 AF XY: 0.000899

Gnomad AFR exome AF: 0.0191

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000644 AC: 941 AN: 1461738 Hom.: 14 Cov.: 32 AF XY: 0.000560 AC XY: 407 AN XY: 727160

African (AFR) AF: 0.0220 AC: 735 AN: 33480

American (AMR) AF: 0.00112 AC: 50 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53314

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5766

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111972

Other (OTH) AF: 0.00151 AC: 91 AN: 60392

GnomAD4 genome AF: 0.00561 AC: 854 AN: 152212 Hom.: 7 Cov.: 32 AF XY: 0.00532 AC XY: 396 AN XY: 74420

African (AFR) AF: 0.0191 AC: 792 AN: 41526

American (AMR) AF: 0.00347 AC: 53 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68000

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00271 Hom.: 5

Bravo AF: 0.00709

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.57
DANN	Benign	0.77
PhyloP100		-1.1
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: rs114583699; hg19: chr1-25254204;