rs2242720

Positions:

• chr21-35341858-A-G
• chr21-35341858-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000475045.6(RUNX1):​c.-197+120103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,086 control chromosomes in the GnomAD database, including 3,999 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 0.22 (3999 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000475045.6	c.-197+120103T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33950 AN: 151968 Hom.: 3997 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.223 AC: 33959 AN: 152086 Hom.: 3999 Cov.: 32 AF XY: 0.221 AC XY: 16443 AN XY: 74340

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.246

Alfa AF: 0.246 Hom.: 9458

Bravo AF: 0.231

Asia WGS AF: 0.224 AC: 779 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	1.0
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242720; hg19: chr21-36714156;