rs2834694

Variant names:

• chr21-34963684-C-A
• rs2834694
• NM_001754.5:c.59-70721G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-34963684-C-A
• chr21-34963684-C-T

Variant summary

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

The NM_001754.5(RUNX1):​c.59-70721G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,982 control chromosomes in the GnomAD database, including 20,479 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 (20479 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.59-70721G>T		intron_variant	Intron 2 of 8	ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.59-70721G>T		intron_variant	Intron 2 of 8		NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78645 AN: 151862 Hom.: 20466 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.518 AC: 78705 AN: 151982 Hom.: 20479 Cov.: 32 AF XY: 0.516 AC XY: 38312 AN XY: 74288

African (AFR) AF: 0.560 AC: 23174 AN: 41412

American (AMR) AF: 0.557 AC: 8515 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2021 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2090 AN: 5160

South Asian (SAS) AF: 0.541 AC: 2604 AN: 4810

European-Finnish (FIN) AF: 0.436 AC: 4608 AN: 10558

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33815 AN: 67970

Other (OTH) AF: 0.518 AC: 1093 AN: 2110

Alfa AF: 0.504 Hom.: 24181

Bravo AF: 0.528

Asia WGS AF: 0.525 AC: 1829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.57
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2834694; hg19: chr21-36335981;