rs11702779

Variant names:

• chr21-34996362-G-A
• rs11702779
• NM_001754.5:c.58+52480C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-34996362-G-A
• chr21-34996362-G-C

Variant summary

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

The NM_001754.5(RUNX1):​c.58+52480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,788 control chromosomes in the GnomAD database, including 11,022 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 0.38 (11022 hom., cov: 31)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.77
• Publications: 17 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.58+52480C>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.58+52480C>T		intron_variant	Intron 2 of 8		NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57369 AN: 151670 Hom.: 10996 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.378 AC: 57440 AN: 151788 Hom.: 11022 Cov.: 31 AF XY: 0.384 AC XY: 28455 AN XY: 74182

African (AFR) AF: 0.358 AC: 14775 AN: 41328

American (AMR) AF: 0.458 AC: 6994 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2320 AN: 5164

South Asian (SAS) AF: 0.419 AC: 2008 AN: 4798

European-Finnish (FIN) AF: 0.403 AC: 4246 AN: 10534

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.362 AC: 24585 AN: 67928

Other (OTH) AF: 0.371 AC: 780 AN: 2102

Alfa AF: 0.370 Hom.: 34366

Bravo AF: 0.383

Asia WGS AF: 0.386 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.049
DANN	Benign	0.40
PhyloP100		-4.8

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: rs11702779; hg19: chr21-36368659;