ENST00000475045.6:c.-771+26394A>G

Variant names:

• chr21-35943681-T-C
• rs2835173
• ENST00000475045.6:c.-771+26394A>G

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-771+26394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,034 control chromosomes in the GnomAD database, including 12,813 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 0.40 (12813 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 2 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 = 0.533 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.-771+26394A>G		intron	N/A	ENSP00000477072.1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60818 AN: 151916 Hom.: 12801 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.400 AC: 60869 AN: 152034 Hom.: 12813 Cov.: 32 AF XY: 0.398 AC XY: 29544 AN XY: 74320

African (AFR) AF: 0.539 AC: 22362 AN: 41460

American (AMR) AF: 0.379 AC: 5797 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3468

East Asian (EAS) AF: 0.464 AC: 2392 AN: 5150

South Asian (SAS) AF: 0.414 AC: 1990 AN: 4806

European-Finnish (FIN) AF: 0.325 AC: 3440 AN: 10576

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22708 AN: 67958

Other (OTH) AF: 0.398 AC: 843 AN: 2116

Alfa AF: 0.362 Hom.: 1263

Bravo AF: 0.410

Asia WGS AF: 0.459 AC: 1592 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.47
PhyloP100		0.074

Splicing

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

Other links and lift over

dbSNP: rs2835173; hg19: chr21-37315979;