dbSNP rs13157: RUNX3:c.*936C>T (chr1-24901186-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004350.3(RUNX3):c.*936C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,806 control chromosomes in the GnomAD database, including 3,332 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 0.15 ( 3332 hom., cov: 30)

Exomes 𝑓: 0.037 ( 0 hom. )

Consequence

RUNX3
NM_004350.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0700

Publications

10 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:

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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=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RUNX3	NM_004350.3	MANE Select	c.*936C>T	3_prime_UTR	Exon 5 of 5	NP_004341.1	Q13761-1
RUNX3	NM_001031680.2		c.*936C>T	3_prime_UTR	Exon 6 of 6	NP_001026850.1	Q13761-2
RUNX3	NM_001320672.1		c.*936C>T	3_prime_UTR	Exon 7 of 7	NP_001307601.1	Q13761-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RUNX3	ENST00000308873.11	TSL:1 MANE Select	c.*936C>T	3_prime_UTR	Exon 5 of 5	ENSP00000308051.6	Q13761-1
RUNX3	ENST00000338888.4	TSL:1	c.*936C>T	3_prime_UTR	Exon 7 of 7	ENSP00000343477.3	Q13761-2
RUNX3	ENST00000399916.5	TSL:2	c.*936C>T	3_prime_UTR	Exon 6 of 6	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22365

AN:

151476

Hom.:

3317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.0815

Gnomad AMR

AF:

0.0686

Gnomad ASJ

AF:

0.0669

Gnomad EAS

AF:

0.0407

Gnomad SAS

AF:

0.0780

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0516

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.0370

AC:

AN:

216

Hom.:

Cov.:

AF XY:

0.0441

AC XY:

AN XY:

136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0294

AC:

AN:

136

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0714

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0238

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.148

AC:

22415

AN:

151590

Hom.:

3332

Cov.:

AF XY:

0.146

AC XY:

10828

AN XY:

74126

show subpopulations

African (AFR)

AF:

0.390

AC:

16054

AN:

41210

American (AMR)

AF:

0.0685

AC:

1046

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0669

AC:

232

AN:

3466

East Asian (EAS)

AF:

0.0408

AC:

210

AN:

5152

South Asian (SAS)

AF:

0.0781

AC:

375

AN:

4802

European-Finnish (FIN)

AF:

0.0603

AC:

634

AN:

10514

Middle Eastern (MID)

AF:

0.131

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0516

AC:

3503

AN:

67888

Other (OTH)

AF:

0.119

AC:

249

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

751

1503

2254

3006

3757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.0759

Hom.:

1564

Bravo

AF:

0.158

Asia WGS

AF:

0.108

AC:

375

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.5

(source)

DANN

Benign

0.38

PhyloP100

0.070

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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