Variant chr21-34788608-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

This summary comes from the ClinGen Evidence Repository: NM_001754.5(RUNX1):c.*3527T>G is a 3' UTR variant. MAF of 0.0001764 (0.01764%, 12/68040) in the European (non-finnish) subpopulation of the gnomAD v3.1.2 cohort is ≥ 0.00015 (0.015%) (BS1). In summary, this variant meets the criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1 LINK:https://erepo.genome.network/evrepo/ui/classification/CA10652908/MONDO:0011071/008

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

RUNX1
NM_001754.5 3_prime_UTR

Scores

Clinical Significance

Likely benign reviewed by expert panel B:2

Conservation

PhyloP100: 4.35

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 Likely_benign. Variant got -4 ACMG points.

BS1

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.*3527T>G		3_prime_UTR_variant	9/9	ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1 linkuse as main transcript	c.*3527T>G	3_prime_UTR_variant	9/9		NM_001754.5	ENSP00000501943	A1	Q01196-8
RUNX1	ENST00000300305.7 linkuse as main transcript	c.*3527T>G	3_prime_UTR_variant	8/8	1		ENSP00000300305	A1	Q01196-8
RUNX1	ENST00000344691.8 linkuse as main transcript	c.*3527T>G	3_prime_UTR_variant	6/6	1		ENSP00000340690	P4	Q01196-1
RUNX1	ENST00000437180.5 linkuse as main transcript	c.*3527T>G	3_prime_UTR_variant	9/9	5		ENSP00000409227	A1	Q01196-8

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

80990

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

37304

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000400

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000401

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000105

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Benign:1

Likely benign, reviewed by expert panel

curation

ClinGen Myeloid Malignancy Variant Curation Expert Panel

Jun 30, 2022

NM_001754.5(RUNX1):c.*3527T>G is a 3' UTR variant. MAF of 0.0001764 (0.01764%, 12/68040) in the European (non-finnish) subpopulation of the gnomAD v3.1.2 cohort is ≥ 0.00015 (0.015%) (BS1). In summary, this variant meets the criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1 -

Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.89

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