chr21-35824604-G-A

Position:

• chr21-35824604-G-A

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-588+39681C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,116 control chromosomes in the GnomAD database, including 2,475 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 0.18 (2475 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 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.-588+39681C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26726 AN: 151998 Hom.: 2464 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.176 AC: 26774 AN: 152116 Hom.: 2475 Cov.: 32 AF XY: 0.179 AC XY: 13296 AN XY: 74342

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.173

Alfa AF: 0.156 Hom.: 902

Bravo AF: 0.177

Asia WGS AF: 0.190 AC: 662 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	1.7
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1883053; hg19: chr21-37196902;