rs2242714

Variant names:

• chr21-35305389-G-A
• rs2242714
• ENST00000475045.6:c.-197+156572C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-35305389-G-A
• chr21-35305389-G-C

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-197+156572C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,884 control chromosomes in the GnomAD database, including 3,015 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 0.19 (3015 hom., cov: 31)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 11 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 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+156572C>T		intron_variant	Intron 9 of 12	5		ENSP00000477072.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29010 AN: 151768 Hom.: 3016 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.191 AC: 29018 AN: 151884 Hom.: 3015 Cov.: 31 AF XY: 0.187 AC XY: 13903 AN XY: 74226

African (AFR) AF: 0.111 AC: 4599 AN: 41434

American (AMR) AF: 0.229 AC: 3497 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1148 AN: 5164

South Asian (SAS) AF: 0.194 AC: 937 AN: 4820

European-Finnish (FIN) AF: 0.158 AC: 1655 AN: 10504

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.229 AC: 15572 AN: 67920

Other (OTH) AF: 0.206 AC: 433 AN: 2106

Alfa AF: 0.219 Hom.: 2160

Bravo AF: 0.196

Asia WGS AF: 0.172 AC: 597 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	1.9
DANN	Benign	0.45
PhyloP100		-0.077

Splicing

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

Other links and lift over

dbSNP: rs2242714; hg19: chr21-36677687;