rs1555884783

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: This synonymous variant is predicted by SSF, MES, and SpliceAI to lead to either no change/an increase/a decrease by no more than 10% in the canonical splice site score and no putative cryptic splice sites are created; in addition, evolutionary conservation prediction algorithms predict the site as not being highly conserved (PhyloP score = 0.223181 in GRCh37/0.744953 in GRCh38 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP4+BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA512232098/MONDO:0011071/008

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

RUNX1
NM_001754.5 synonymous

Scores

2

Clinical Significance

Likely benign reviewed by expert panel B:3

Conservation

PhyloP100: 0.855

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

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
RUNX1NM_001754.5 linkc.1440C>T p.Tyr480Tyr synonymous_variant Exon 9 of 9 ENST00000675419.1 NP_001745.2 Q01196-8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RUNX1ENST00000675419.1 linkc.1440C>T p.Tyr480Tyr synonymous_variant Exon 9 of 9 NM_001754.5 ENSP00000501943.1 Q01196-8

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151460
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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
GnomAD4 exome
AF:
7.56e-7
AC:
1
AN:
1322180
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
648790
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
27300
American (AMR)
AF:
0.00
AC:
0
AN:
26942
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20954
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33568
South Asian (SAS)
AF:
0.00
AC:
0
AN:
69702
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
31460
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3822
European-Non Finnish (NFE)
AF:
9.49e-7
AC:
1
AN:
1053504
Other (OTH)
AF:
0.00
AC:
0
AN:
54928
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000660
AC:
1
AN:
151460
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
73982
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41380
American (AMR)
AF:
0.00
AC:
0
AN:
15194
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3464
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5146
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10342
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67798
Other (OTH)
AF:
0.00
AC:
0
AN:
2078
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
May 29, 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
Jan 12, 2021
ClinGen Myeloid Malignancy Variant Curation Expert Panel
Significance:Likely benign
Review Status:reviewed by expert panel
Collection Method:curation

This synonymous variant is predicted by SSF, MES, and SpliceAI to lead to either no change/an increase/a decrease by no more than 10% in the canonical splice site score and no putative cryptic splice sites are created; in addition, evolutionary conservation prediction algorithms predict the site as not being highly conserved (PhyloP score = 0.223181 in GRCh37/0.744953 in GRCh38 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP4+BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and BP7. -

Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Benign:1
Oct 24, 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
-0.66
CADD
Benign
5.3
DANN
Benign
0.95
PhyloP100
0.85

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

Other links and lift over

dbSNP: rs1555884783; hg19: chr21-36164435; API