Genetic Variant RUNX3:c.283-96G>A (chr1-24927826-C-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_004350.3(RUNX3):c.283-96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,062,078 control chromosomes in the GnomAD database, including 166,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.53 ( 21523 hom., cov: 32)

Exomes 𝑓: 0.56 ( 145048 hom. )

Consequence

RUNX3
NM_004350.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.67

Publications

23 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-24927826-C-T is Benign according to our data. Variant chr1-24927826-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688389.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 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.283-96G>A	intron	N/A	NP_004341.1	Q13761-1
RUNX3	NM_001031680.2		c.325-96G>A	intron	N/A	NP_001026850.1	Q13761-2
RUNX3	NM_001320672.1		c.325-96G>A	intron	N/A	NP_001307601.1	Q13761-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RUNX3	ENST00000308873.11	TSL:1 MANE Select	c.283-96G>A	intron	N/A	ENSP00000308051.6	Q13761-1
RUNX3	ENST00000338888.4	TSL:1	c.325-96G>A	intron	N/A	ENSP00000343477.3	Q13761-2
RUNX3	ENST00000399916.5	TSL:2	c.325-96G>A	intron	N/A	ENSP00000382800.1	Q13761-2

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80426

AN:

151894

Hom.:

21481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.708

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.538

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.525

GnomAD4 exome

AF:

0.562

AC:

511551

AN:

910066

Hom.:

145048

AF XY:

0.562

AC XY:

262980

AN XY:

468180

show subpopulations

African (AFR)

AF:

0.457

AC:

10520

AN:

23002

American (AMR)

AF:

0.631

AC:

26019

AN:

41226

Ashkenazi Jewish (ASJ)

AF:

0.526

AC:

10860

AN:

20652

East Asian (EAS)

AF:

0.547

AC:

20100

AN:

36742

South Asian (SAS)

AF:

0.574

AC:

40396

AN:

70400

European-Finnish (FIN)

AF:

0.554

AC:

27540

AN:

49674

Middle Eastern (MID)

AF:

0.491

AC:

2238

AN:

4558

European-Non Finnish (NFE)

AF:

0.564

AC:

350786

AN:

622048

Other (OTH)

AF:

0.553

AC:

23092

AN:

41764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

10968

21936

32905

43873

54841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7496

14992

22488

29984

37480

<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:

0.530

AC:

80523

AN:

152012

Hom.:

21523

Cov.:

AF XY:

0.528

AC XY:

39232

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.458

AC:

18988

AN:

41462

American (AMR)

AF:

0.558

AC:

8527

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.538

AC:

1865

AN:

3468

East Asian (EAS)

AF:

0.518

AC:

2681

AN:

5178

South Asian (SAS)

AF:

0.576

AC:

2777

AN:

4818

European-Finnish (FIN)

AF:

0.565

AC:

5962

AN:

10558

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.557

AC:

37841

AN:

67940

Other (OTH)

AF:

0.520

AC:

1094

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1961

3922

5883

7844

9805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.550

Hom.:

20554

Bravo

AF:

0.534

Asia WGS

AF:

0.505

AC:

1752

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

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.75

(source)

DANN

Benign

0.49

PhyloP100

-1.7

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