rs2247614

Variant names:

• chr21-35259389-G-C
• rs2247614
• ENST00000475045.6:c.-196-194317C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-35259389-G-C
• chr21-35259389-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.-196-194317C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,210 control chromosomes in the GnomAD database, including 1,600 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 0.14 (1600 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 1 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, Ambry Genetics, G2P
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000475045.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	ENST00000475045.6	TSL:5	c.-196-194317C>G		intron	N/A	ENSP00000477072.1	V9GYT5

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21087 AN: 152090 Hom.: 1600 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.139 AC: 21105 AN: 152210 Hom.: 1600 Cov.: 32 AF XY: 0.138 AC XY: 10242 AN XY: 74432

African (AFR) AF: 0.192 AC: 7980 AN: 41508

American (AMR) AF: 0.109 AC: 1665 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1229 AN: 5170

South Asian (SAS) AF: 0.131 AC: 633 AN: 4830

European-Finnish (FIN) AF: 0.0980 AC: 1041 AN: 10620

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7601 AN: 68004

Other (OTH) AF: 0.157 AC: 331 AN: 2112

Alfa AF: 0.0632 Hom.: 64

Bravo AF: 0.146

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.73
DANN	Benign	0.36
PhyloP100		0.028

Splicing

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

Other links and lift over

dbSNP: rs2247614; hg19: chr21-36631687;