chr21-34788414-T-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001754.5(RUNX1):c.*3721A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 233,042 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.0016 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 1 hom. )
Consequence
RUNX1
NM_001754.5 3_prime_UTR
NM_001754.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0480
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 21-34788414-T-A is Benign according to our data. Variant chr21-34788414-T-A is described in ClinVar as [Benign]. Clinvar id is 339801.Status of the report is reviewed_by_expert_panel, 3 stars.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0012 (97/80726) while in subpopulation MID AF= 0.0225 (11/488). AF 95% confidence interval is 0.0126. There are 1 homozygotes in gnomad4_exome. There are 61 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
?
High AC in GnomAd at 250 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RUNX1 | NM_001754.5 | c.*3721A>T | 3_prime_UTR_variant | 9/9 | ENST00000675419.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RUNX1 | ENST00000675419.1 | c.*3721A>T | 3_prime_UTR_variant | 9/9 | NM_001754.5 | A1 | |||
RUNX1 | ENST00000300305.7 | c.*3721A>T | 3_prime_UTR_variant | 8/8 | 1 | A1 | |||
RUNX1 | ENST00000344691.8 | c.*3721A>T | 3_prime_UTR_variant | 6/6 | 1 | P4 | |||
RUNX1 | ENST00000437180.5 | c.*3721A>T | 3_prime_UTR_variant | 9/9 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00164 AC: 250AN: 152198Hom.: 8 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
250
AN:
152198
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00120 AC: 97AN: 80726Hom.: 1 Cov.: 0 AF XY: 0.00164 AC XY: 61AN XY: 37188
GnomAD4 exome
AF:
AC:
97
AN:
80726
Hom.:
Cov.:
0
AF XY:
AC XY:
61
AN XY:
37188
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00163 AC: 249AN: 152316Hom.: 8 Cov.: 32 AF XY: 0.00148 AC XY: 110AN XY: 74484
GnomAD4 genome
?
AF:
AC:
249
AN:
152316
Hom.:
Cov.:
32
AF XY:
AC XY:
110
AN XY:
74484
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Benign:1
Benign, reviewed by expert panel | curation | ClinGen Myeloid Malignancy Variant Curation Expert Panel | May 13, 2020 | The c.*3721A>T variant in the 3' UTR has an MAF of 0.001757 (0.18%, 24/13660 alleles) in the Latino subpopulation of the gnomAD v3 cohort and is >= 0.0015 (0.15%) (BA1). This variant is detected in a homozygous state in 8 Amish individuals in the gnomAD v3 population database (BP2). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP2. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at