rs2003624

Variant names:

• chr21-35603175-G-C
• rs2003624
• ENST00000475045.6:c.-531-22246C>G

Your query was ambiguous. Multiple possible variants found:

• chr21-35603175-G-C
• chr21-35603175-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.-531-22246C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,122 control chromosomes in the GnomAD database, including 18,043 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 0.48 (18043 hom., cov: 33)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 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.-531-22246C>G		intron_variant	Intron 7 of 12	5		ENSP00000477072.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73435 AN: 152004 Hom.: 18019 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.483 AC: 73484 AN: 152122 Hom.: 18043 Cov.: 33 AF XY: 0.483 AC XY: 35946 AN XY: 74366

African (AFR) AF: 0.563 AC: 23364 AN: 41514

American (AMR) AF: 0.419 AC: 6409 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3468

East Asian (EAS) AF: 0.588 AC: 3040 AN: 5166

South Asian (SAS) AF: 0.529 AC: 2550 AN: 4818

European-Finnish (FIN) AF: 0.465 AC: 4922 AN: 10588

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30336 AN: 67956

Other (OTH) AF: 0.454 AC: 959 AN: 2114

Alfa AF: 0.333 Hom.: 873

Bravo AF: 0.479

Asia WGS AF: 0.540 AC: 1878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.45
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs2003624; hg19: chr21-36975473;