ENST00000475045.6:c.-197+142806C>T

Variant names:

• chr21-35319155-G-A
• rs732569
• ENST00000475045.6:c.-197+142806C>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+142806C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,984 control chromosomes in the GnomAD database, including 21,736 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 0.51 (21736 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 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+142806C>T		intron_variant	Intron 9 of 12	5		ENSP00000477072.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77836 AN: 151866 Hom.: 21714 Cov.: 32

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.513 AC: 77904 AN: 151984 Hom.: 21736 Cov.: 32 AF XY: 0.508 AC XY: 37698 AN XY: 74270

African (AFR) AF: 0.752 AC: 31210 AN: 41480

American (AMR) AF: 0.405 AC: 6194 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1486 AN: 3464

East Asian (EAS) AF: 0.302 AC: 1559 AN: 5164

South Asian (SAS) AF: 0.386 AC: 1859 AN: 4814

European-Finnish (FIN) AF: 0.440 AC: 4618 AN: 10504

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29447 AN: 67960

Other (OTH) AF: 0.488 AC: 1032 AN: 2114

Alfa AF: 0.479 Hom.: 4260

Bravo AF: 0.521

Asia WGS AF: 0.369 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.64
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs732569; hg19: chr21-36691453;