Genetic Variant RUNX3:c.58+1271G>C (chr1-24963243-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001031680.2(RUNX3):c.58+1271G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,452 control chromosomes in the GnomAD database, including 17,659 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 0.46 ( 17627 hom., cov: 33)

Exomes 𝑓: 0.44 ( 32 hom. )

Consequence

RUNX3
NM_001031680.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

14 publications found

Variant links:

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 links:

RUNX3-AS1 (HGNC:40513): (RUNX3 antisense RNA 1)

RUNX3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031680.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
RUNX3	NM_001031680.2	c.58+1271G>C	intron	N/A	NP_001026850.1	Q13761-2
RUNX3	NM_001320672.1	c.58+1271G>C	intron	N/A	NP_001307601.1	Q13761-2
RUNX3-AS1	NR_183339.1	n.2562C>G	non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RUNX3	ENST00000338888.4	TSL:1	c.58+1271G>C	intron	N/A	ENSP00000343477.3	Q13761-2
RUNX3	ENST00000479341.1	TSL:1	n.168+1271G>C	intron	N/A
RUNX3	ENST00000399916.5	TSL:2	c.58+1271G>C	intron	N/A	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69748

AN:

151998

Hom.:

17606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.651

Gnomad AMR

AF:

0.632

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.705

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.488

GnomAD4 exome

AF:

0.440

AC:

148

AN:

336

Hom.:

AF XY:

0.437

AC XY:

104

AN XY:

238

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.833

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.417

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.424

AC:

118

AN:

278

Other (OTH)

AF:

0.571

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.459

AC:

69777

AN:

152116

Hom.:

17627

Cov.:

AF XY:

0.472

AC XY:

35092

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.244

AC:

10106

AN:

41496

American (AMR)

AF:

0.633

AC:

9682

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1737

AN:

3468

East Asian (EAS)

AF:

0.704

AC:

3642

AN:

5170

South Asian (SAS)

AF:

0.589

AC:

2838

AN:

4820

European-Finnish (FIN)

AF:

0.575

AC:

6083

AN:

10576

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.499

AC:

33906

AN:

67970

Other (OTH)

AF:

0.493

AC:

1042

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1820

3640

5459

7279

9099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.476

Hom.:

2256

Bravo

AF:

0.455

Asia WGS

AF:

0.648

AC:

2251

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

5.5

(source)

DANN

Benign

0.58

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over