ENST00000475045.6:c.-197+139652C>T

Variant names:

• chr21-35322309-G-A
• rs2834908
• ENST00000475045.6:c.-197+139652C>T

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-197+139652C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,642 control chromosomes in the GnomAD database, including 22,834 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 0.52 (22834 hom., cov: 31)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000475045.6	c.-197+139652C>T		intron_variant	Intron 9 of 12	5		ENSP00000477072.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79484 AN: 151524 Hom.: 22801 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.525 AC: 79564 AN: 151642 Hom.: 22834 Cov.: 31 AF XY: 0.520 AC XY: 38509 AN XY: 74084

African (AFR) AF: 0.780 AC: 32299 AN: 41392

American (AMR) AF: 0.424 AC: 6458 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1578 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1524 AN: 5134

South Asian (SAS) AF: 0.419 AC: 2013 AN: 4804

European-Finnish (FIN) AF: 0.429 AC: 4491 AN: 10472

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29618 AN: 67806

Other (OTH) AF: 0.508 AC: 1073 AN: 2112

Alfa AF: 0.445 Hom.: 8028

Bravo AF: 0.536

Asia WGS AF: 0.380 AC: 1323 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.66
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs2834908; hg19: chr21-36694607;