rs200907577

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BP7

This summary comes from the ClinGen Evidence Repository: NM_001754.5(RUNX1):c.492C>T (p.Val164=) is a synonymous variant. No REVEL score because a synonymous variant and SpliceAI is ≤0.20( 0.01 Donor Loss -16bp and 0.11 Donor Gain 7bp) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP 1.91014 ≤ 2.0) meeting 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 and BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA10014503/MONDO:0011071/008

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

RUNX1
NM_001754.5 synonymous

Scores

2

Clinical Significance

Likely benign reviewed by expert panel U:1B:4

Conservation

PhyloP100: 1.93
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]
ENSG00000286153 (HGNC:56821): (RUNX1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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.492C>T p.Val164Val synonymous_variant Exon 5 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.492C>T p.Val164Val synonymous_variant Exon 5 of 9 NM_001754.5 ENSP00000501943.1 Q01196-8

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152110
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000103
AC:
26
AN:
251404
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00179
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000493
AC:
72
AN:
1461806
Hom.:
0
Cov.:
31
AF XY:
0.0000454
AC XY:
33
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00115
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000234
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152110
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.0000907
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Uncertain:1Benign:4
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 26, 2019
Genetic Services Laboratory, University of Chicago
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Benign:1
Jul 05, 2022
ClinGen Myeloid Malignancy Variant Curation Expert Panel
Significance: Likely benign
Review Status: reviewed by expert panel
Collection Method: curation

NM_001754.5(RUNX1):c.492C>T (p.Val164=) is a synonymous variant. No REVEL score because a synonymous variant and SpliceAI is ≤0.20( 0.01 Donor Loss -16bp and 0.11 Donor Gain 7bp) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP 1.91014 ≤ 2.0) meeting 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 and BP7. -

Hereditary cancer-predisposing syndrome Benign:1
May 29, 2020
Sema4, Sema4
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: curation

- -

Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Benign:1
Dec 16, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Acute myeloid leukemia Benign:1
Jul 07, 2023
KCCC/NGS Laboratory, Kuwait Cancer Control Center
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
-0.26
CADD
Benign
17
DANN
Benign
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200907577; hg19: chr21-36252870; API