rs766678402

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP7BP4

This summary comes from the ClinGen Evidence Repository: The variant NM_001754.5(RUNX1): c.1119G>C (p.Ser373=) is a synonymous variant. As this is a synonymous variant, there is no REVEL score however SpliceAI is ≤0.20 (0.00) (BP4). The PhyloP score is <2.0 (-0.771) (BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7 LINK:https://erepo.genome.network/evrepo/ui/classification/CA10014198/MONDO:0011071/008

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

RUNX1
NM_001754.5 synonymous

Scores

Clinical Significance

Likely benign reviewed by expert panel B:3

Conservation

PhyloP100: 0.0170

Publications

0 publications found

Variant links:

Genes affected

RUNX1 (HGNC:10471): (RUNX family transcription factor 1) Core binding factor (CBF) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters. The protein encoded by this gene represents the alpha subunit of CBF and is thought to be involved in the development of normal hematopoiesis. Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RUNX1 Gene-Disease associations (from GenCC):

hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
acute myeloid leukemia
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

RUNX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

For more information check the summary or visit ClinGen Evidence Repository.

BP7

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX1	NM_001754.5 link	c.1119G>C	p.Ser373Ser	synonymous_variant	Exon 9 of 9	ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1 link	c.1119G>C	p.Ser373Ser	synonymous_variant	Exon 9 of 9		NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000106

AC:

AN:

188544

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000253

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000840

AC:

AN:

1428264

Hom.:

Cov.:

AF XY:

0.00000707

AC XY:

AN XY:

707210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32882

American (AMR)

AF:

0.00

AC:

AN:

39274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25482

East Asian (EAS)

AF:

0.00

AC:

AN:

37984

South Asian (SAS)

AF:

0.00

AC:

AN:

81858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50558

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00000913

AC:

AN:

1095374

Other (OTH)

AF:

0.0000169

AC:

AN:

59132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Jan 16, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Benign:1

Feb 11, 2022

ClinGen Myeloid Malignancy Variant Curation Expert Panel

Significance:Likely benign

Review Status:reviewed by expert panel

Collection Method:curation

The variant NM_001754.5(RUNX1): c.1119G>C (p.Ser373=) is a synonymous variant. As this is a synonymous variant, there is no REVEL score however SpliceAI is ≤0.20 (0.00) (BP4). The PhyloP score is <2.0 (-0.771) (BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7 -

Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Benign:1

Jun 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.5

(source)

DANN

Benign

0.79

PhyloP100

0.017

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over