ENST00000475045.6:c.-262+55100T>C

Variant names:

• chr21-35525560-A-G
• rs445984
• ENST00000475045.6:c.-262+55100T>C

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-262+55100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,986 control chromosomes in the GnomAD database, including 11,811 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 0.39 (11811 hom., cov: 31)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31
• Publications: 4 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, Ambry Genetics, G2P
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

LOC100506403 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100506403	NR_073512.1		n.105+55100T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	ENST00000475045.6	TSL:5	c.-262+55100T>C		intron	N/A	ENSP00000477072.1	V9GYT5
	RUNX1	ENST00000467692.5	TSL:2	n.101+55100T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58864 AN: 151868 Hom.: 11787 Cov.: 31

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.388 AC: 58933 AN: 151986 Hom.: 11811 Cov.: 31 AF XY: 0.386 AC XY: 28652 AN XY: 74280

African (AFR) AF: 0.313 AC: 12961 AN: 41456

American (AMR) AF: 0.422 AC: 6443 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1468 AN: 3468

East Asian (EAS) AF: 0.171 AC: 883 AN: 5170

South Asian (SAS) AF: 0.367 AC: 1762 AN: 4806

European-Finnish (FIN) AF: 0.387 AC: 4084 AN: 10556

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29861 AN: 67948

Other (OTH) AF: 0.410 AC: 865 AN: 2112

Alfa AF: 0.387 Hom.: 1997

Bravo AF: 0.385

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.19
PhyloP100		-3.3

Splicing

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

Other links and lift over

dbSNP: rs445984; hg19: chr21-36897858;