rs8133843

Variant names:

• chr21-35365944-G-A
• rs8133843
• ENST00000475045.6:c.-197+96017C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-35365944-G-A
• chr21-35365944-G-C
• chr21-35365944-G-T

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-197+96017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,988 control chromosomes in the GnomAD database, including 31,798 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 0.65 (31798 hom., cov: 33)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 20 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

ENSG00000309377 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 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.-197+96017C>T		intron_variant	Intron 9 of 12	5		ENSP00000477072.1
ENSG00000309377	ENST00000840639.1	n.69-15814C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97986 AN: 151870 Hom.: 31759 Cov.: 33

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.645 AC: 98088 AN: 151988 Hom.: 31798 Cov.: 33 AF XY: 0.646 AC XY: 47960 AN XY: 74254

African (AFR) AF: 0.710 AC: 29474 AN: 41492

American (AMR) AF: 0.633 AC: 9665 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2284 AN: 3466

East Asian (EAS) AF: 0.526 AC: 2717 AN: 5164

South Asian (SAS) AF: 0.635 AC: 3062 AN: 4820

European-Finnish (FIN) AF: 0.651 AC: 6845 AN: 10516

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.617 AC: 41954 AN: 67946

Other (OTH) AF: 0.624 AC: 1317 AN: 2112

Alfa AF: 0.631 Hom.: 42729

Bravo AF: 0.647

Asia WGS AF: 0.575 AC: 1991 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.10
DANN	Benign	0.26
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs8133843; hg19: chr21-36738242;