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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_004350.3 link	c.*936C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000308873.11	NP_004341.1	Q13761-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RUNX3	ENST00000308873.11 link	c.*936C>T	3_prime_UTR_variant	Exon 5 of 5	1	NM_004350.3	ENSP00000308051.6	Q13761-1
RUNX3	ENST00000338888.4 link	c.*936C>T	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000343477.3	Q13761-2
RUNX3	ENST00000399916.5 link	c.*936C>T	3_prime_UTR_variant	Exon 6 of 6	2		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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over