rs9979153

Variant names:

• chr21-34951210-C-T
• rs9979153
• NM_001754.5:c.59-58247G>A

Variant summary

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

The NM_001754.5(RUNX1):​c.59-58247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 152,228 control chromosomes in the GnomAD database, including 507 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 0.069 (507 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.59-58247G>A		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.59-58247G>A		intron_variant	Intron 2 of 8		NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.0694 AC: 10560 AN: 152110 Hom.: 507 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.0328

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0406

Gnomad OTH AF: 0.0680

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

GnomAD4 genome AF: 0.0694 AC: 10563 AN: 152228 Hom.: 507 Cov.: 32 AF XY: 0.0696 AC XY: 5178 AN XY: 74418

African (AFR) AF: 0.120 AC: 4986 AN: 41526

American (AMR) AF: 0.0910 AC: 1392 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3468

East Asian (EAS) AF: 0.0533 AC: 276 AN: 5174

South Asian (SAS) AF: 0.0332 AC: 160 AN: 4820

European-Finnish (FIN) AF: 0.0670 AC: 710 AN: 10594

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0405 AC: 2757 AN: 68030

Other (OTH) AF: 0.0678 AC: 143 AN: 2110

Alfa AF: 0.0512 Hom.: 533

Bravo AF: 0.0755

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.61
PhyloP100		0.026

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: rs9979153; hg19: chr21-36323507;