Variant 21-34792108-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BA1BP2

This summary comes from the ClinGen Evidence Repository: The NM_001754.4:c.*27C>A variant in the 3' UTR has an MAF of 0.4444 (44%, 1352/3042 alleles) in the South Asian subpopulation of the gnomAD v3 cohort and is ≥ 0.0015 (0.15%) (BA1). This variant is detected in a homozygous state in 301 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. LINK:https://erepo.genome.network/evrepo/ui/classification/CA10014168/MONDO:0011071/008

Frequency

Genomes: 𝑓 0.37 ( 10586 hom., cov: 31)

Exomes 𝑓: 0.43 ( 109377 hom. )

Consequence

RUNX1
NM_001754.5 3_prime_UTR

Scores

Clinical Significance

Benign reviewed by expert panel B:6

Conservation

PhyloP100: 0.391

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP2

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

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1	NM_001754.5 linkuse as main transcript	c.*27C>A		3_prime_UTR_variant	9/9	ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1 linkuse as main transcript	c.*27C>A		3_prime_UTR_variant	9/9		NM_001754.5	ENSP00000501943	A1	Q01196-8

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55035

AN:

150170

Hom.:

10588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.452

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.364

GnomAD3 exomes

AF:

0.485

AC:

3719

AN:

7666

Hom.:

899

AF XY:

0.486

AC XY:

2261

AN XY:

4648

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.496

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

0.403

Gnomad SAS exome

AF:

0.516

Gnomad FIN exome

AF:

0.519

Gnomad NFE exome

AF:

0.485

Gnomad OTH exome

AF:

0.531

GnomAD4 exome

AF:

0.427

AC:

505328

AN:

1183120

Hom.:

109377

Cov.:

AF XY:

0.428

AC XY:

245121

AN XY:

573334

show subpopulations

Gnomad4 AFR exome

AF:

0.224

Gnomad4 AMR exome

AF:

0.381

Gnomad4 ASJ exome

AF:

0.395

Gnomad4 EAS exome

AF:

0.377

Gnomad4 SAS exome

AF:

0.453

Gnomad4 FIN exome

AF:

0.468

Gnomad4 NFE exome

AF:

0.433

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.366

AC:

55043

AN:

150276

Hom.:

10586

Cov.:

AF XY:

0.369

AC XY:

27065

AN XY:

73432

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.392

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.452

Gnomad4 NFE

AF:

0.426

Gnomad4 OTH

AF:

0.367

Alfa

AF:

0.266

Hom.:

693

Bravo

AF:

0.355

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 03, 2014

- -

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 NM_001754.4:c.*27C>A variant in the 3' UTR has an MAF of 0.4444 (44%, 1352/3042 alleles) in the South Asian subpopulation of the gnomAD v3 cohort and is >= 0.0015 (0.15%) (BA1). This variant is detected in a homozygous state in 301 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.1

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over