rs1883053

Variant names:

• chr21-35824604-G-A
• rs1883053
• ENST00000475045.6:c.-588+39681C>T

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-588+39681C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,116 control chromosomes in the GnomAD database, including 2,475 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 0.18 (2475 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 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.-588+39681C>T		intron_variant	Intron 6 of 12	5		ENSP00000477072.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26726 AN: 151998 Hom.: 2464 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.176 AC: 26774 AN: 152116 Hom.: 2475 Cov.: 32 AF XY: 0.179 AC XY: 13296 AN XY: 74342

African (AFR) AF: 0.206 AC: 8536 AN: 41498

American (AMR) AF: 0.215 AC: 3277 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1124 AN: 5170

South Asian (SAS) AF: 0.216 AC: 1039 AN: 4810

European-Finnish (FIN) AF: 0.180 AC: 1911 AN: 10592

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.148 AC: 10056 AN: 67986

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.155 Hom.: 1005

Bravo AF: 0.177

Asia WGS AF: 0.190 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs1883053; hg19: chr21-37196902;