rs760061

Variant names:

• chr21-35682209-T-C
• rs760061
• ENST00000475045.6:c.-587-27334A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000475045.6(RUNX1):​c.-587-27334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,070 control chromosomes in the GnomAD database, including 9,418 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9418 hom., cov: 31)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000475045.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	ENST00000475045.6	TSL:5	c.-587-27334A>G		intron	N/A	ENSP00000477072.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52238 AN: 151952 Hom.: 9395 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.366

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.344 AC: 52313 AN: 152070 Hom.: 9418 Cov.: 31 AF XY: 0.340 AC XY: 25309 AN XY: 74332

African (AFR) AF: 0.249 AC: 10310 AN: 41458

American (AMR) AF: 0.379 AC: 5800 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1257 AN: 3468

East Asian (EAS) AF: 0.159 AC: 824 AN: 5174

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4824

European-Finnish (FIN) AF: 0.353 AC: 3733 AN: 10578

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27818 AN: 67970

Other (OTH) AF: 0.366 AC: 771 AN: 2104

Alfa AF: 0.389 Hom.: 10328

Bravo AF: 0.340

Asia WGS AF: 0.221 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.81
PhyloP100		0.53

Splicing

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

Other links and lift over

dbSNP: rs760061; hg19: chr21-37054507;