ENST00000475045.6:c.-197+160686G>A

Variant names:

• chr21-35301275-C-T
• rs10483028
• ENST00000475045.6:c.-197+160686G>A

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-197+160686G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,090 control chromosomes in the GnomAD database, including 2,934 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 0.19 (2934 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	ENST00000475045.6	TSL:5	c.-197+160686G>A		intron	N/A	ENSP00000477072.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28358 AN: 151972 Hom.: 2935 Cov.: 32

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.187 AC: 28366 AN: 152090 Hom.: 2934 Cov.: 32 AF XY: 0.183 AC XY: 13617 AN XY: 74356

African (AFR) AF: 0.0961 AC: 3984 AN: 41464

American (AMR) AF: 0.227 AC: 3469 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5170

South Asian (SAS) AF: 0.196 AC: 946 AN: 4824

European-Finnish (FIN) AF: 0.157 AC: 1664 AN: 10584

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15590 AN: 67982

Other (OTH) AF: 0.201 AC: 425 AN: 2116

Alfa AF: 0.221 Hom.: 16346

Bravo AF: 0.191

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.51
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs10483028; hg19: chr21-36673573;