rs2834902

Variant names:

• chr21-35316230-A-C
• rs2834902
• ENST00000475045.6:c.-197+145731T>G

Your query was ambiguous. Multiple possible variants found:

• chr21-35316230-A-C
• chr21-35316230-A-G

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-197+145731T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,158 control chromosomes in the GnomAD database, including 39,836 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 0.72 (39836 hom., cov: 34)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 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+145731T>G		intron_variant	Intron 9 of 12	5		ENSP00000477072.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109728 AN: 152040 Hom.: 39796 Cov.: 34

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.722 AC: 109818 AN: 152158 Hom.: 39836 Cov.: 34 AF XY: 0.718 AC XY: 53365 AN XY: 74366

African (AFR) AF: 0.753 AC: 31257 AN: 41510

American (AMR) AF: 0.657 AC: 10049 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2481 AN: 3472

East Asian (EAS) AF: 0.713 AC: 3687 AN: 5168

South Asian (SAS) AF: 0.722 AC: 3480 AN: 4822

European-Finnish (FIN) AF: 0.679 AC: 7177 AN: 10572

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49150 AN: 68004

Other (OTH) AF: 0.733 AC: 1552 AN: 2116

Alfa AF: 0.723 Hom.: 76603

Bravo AF: 0.726

Asia WGS AF: 0.704 AC: 2444 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	0.27
DANN	Benign	0.49
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs2834902; hg19: chr21-36688528;