Genetic Variant ENST00000338888.4: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 ENST00000338888.4(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
ENST00000338888.4 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
RUNX3-AS1	NR_183339.1 link	n.2562C>G	non_coding_transcript_exon_variant	Exon 6 of 6
RUNX3-AS1	NR_183340.1 link	n.2334C>G	non_coding_transcript_exon_variant	Exon 4 of 4
RUNX3-AS1	NR_183341.1 link	n.2102C>G	non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
RUNX3	ENST00000338888.4 link	c.58+1271G>C	intron_variant	Intron 2 of 6	1	ENSP00000343477.3	Q13761-2
RUNX3	ENST00000479341.1 link	n.168+1271G>C	intron_variant	Intron 2 of 2	1
RUNX3	ENST00000399916.5 link	c.58+1271G>C	intron_variant	Intron 1 of 5	2	ENSP00000382800.1	Q13761-2
RUNX3-AS1	ENST00000456316.1 link	n.*146C>G	downstream_gene_variant		5

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over