dbSNP rs6672420: RUNX3:p.Ile18Asn (chr1-24964519-A-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001031680.2(RUNX3):c.53T>A(p.Ile18Asn) variant causes a missense change. The variant allele was found at a frequency of 0.504 in 1,608,192 control chromosomes in the GnomAD database, including 208,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 19749 hom., cov: 32)

Exomes 𝑓: 0.50 ( 189230 hom. )

Consequence

RUNX3
NM_001031680.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.82

Publications

61 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6813297E-5).

BP6

Variant 1-24964519-A-T is Benign according to our data. Variant chr1-24964519-A-T is described in ClinVar as Benign. ClinVar VariationId is 2688533.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 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	HGVSp	Effect	Exon Rank	Protein	UniProt
RUNX3	NM_001031680.2	c.53T>A	p.Ile18Asn	missense	Exon 1 of 6	NP_001026850.1	Q13761-2
RUNX3	NM_001320672.1	c.53T>A	p.Ile18Asn	missense	Exon 2 of 7	NP_001307601.1	Q13761-2
RUNX3-AS1	NR_183339.1	n.3838A>T		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUNX3	ENST00000338888.4	TSL:1	c.53T>A	p.Ile18Asn	missense	Exon 2 of 7	ENSP00000343477.3	Q13761-2
RUNX3	ENST00000479341.1	TSL:1	n.163T>A		non_coding_transcript_exon	Exon 2 of 3
RUNX3	ENST00000399916.5	TSL:2	c.53T>A	p.Ile18Asn	missense	Exon 1 of 6	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76330

AN:

151844

Hom.:

19720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.651

Gnomad AMR

AF:

0.647

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.709

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.533

GnomAD2 exomes

AF:

0.560

AC:

135790

AN:

242600

AF XY:

0.559

show subpopulations

Gnomad AFR exome

AF:

0.421

Gnomad AMR exome

AF:

0.751

Gnomad ASJ exome

AF:

0.505

Gnomad EAS exome

AF:

0.711

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.475

Gnomad OTH exome

AF:

0.542

GnomAD4 exome

AF:

0.504

AC:

734217

AN:

1456230

Hom.:

189230

Cov.:

AF XY:

0.508

AC XY:

368166

AN XY:

724028

show subpopulations

African (AFR)

AF:

0.421

AC:

14055

AN:

33360

American (AMR)

AF:

0.740

AC:

32757

AN:

44238

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

13245

AN:

26048

East Asian (EAS)

AF:

0.659

AC:

25993

AN:

39472

South Asian (SAS)

AF:

0.667

AC:

56932

AN:

85294

European-Finnish (FIN)

AF:

0.526

AC:

27901

AN:

53026

Middle Eastern (MID)

AF:

0.573

AC:

3295

AN:

5754

European-Non Finnish (NFE)

AF:

0.477

AC:

528717

AN:

1108888

Other (OTH)

AF:

0.521

AC:

31322

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

17020

34040

51059

68079

85099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15844

31688

47532

63376

79220

<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:

0.503

AC:

76384

AN:

151962

Hom.:

19749

Cov.:

AF XY:

0.515

AC XY:

38268

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.425

AC:

17583

AN:

41412

American (AMR)

AF:

0.647

AC:

9895

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

1749

AN:

3468

East Asian (EAS)

AF:

0.709

AC:

3662

AN:

5166

South Asian (SAS)

AF:

0.669

AC:

3222

AN:

4816

European-Finnish (FIN)

AF:

0.536

AC:

5663

AN:

10568

Middle Eastern (MID)

AF:

0.541

AC:

158

AN:

292

European-Non Finnish (NFE)

AF:

0.482

AC:

32726

AN:

67942

Other (OTH)

AF:

0.538

AC:

1132

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1922

3844

5767

7689

9611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.494

Hom.:

6071

Bravo

AF:

0.509

TwinsUK

AF:

0.481

AC:

1785

ALSPAC

AF:

0.456

AC:

1757

ESP6500AA

AF:

0.424

AC:

1866

ESP6500EA

AF:

0.484

AC:

4162

ExAC

AF:

0.543

AC:

65816

Asia WGS

AF:

0.694

AC:

2414

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Benign

0.97

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.70

MetaRNN

Benign

0.000017

MetaSVM

Benign

-0.90

PhyloP100

5.8

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.48

Sift

Uncertain

0.013

Sift4G

Benign

0.26

Polyphen

1.0

Vest4

0.36

MPC

2.1

ClinPred

0.051

GERP RS

5.7

PromoterAI

-0.011

Neutral

(source)

gMVP

0.30

Mutation Taster

=71/29

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