21-35050181-C-T

Position:

• chr21-35050181-C-T

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-59-1223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,048 control chromosomes in the GnomAD database, including 4,372 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 (4372 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000475045.6	c.-59-1223G>A		intron_variant		5		ENSP00000477072

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33444 AN: 151930 Hom.: 4371 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.220 AC: 33493 AN: 152048 Hom.: 4372 Cov.: 32 AF XY: 0.219 AC XY: 16303 AN XY: 74318

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.208

Alfa AF: 0.165 Hom.: 2470

Bravo AF: 0.234

Asia WGS AF: 0.242 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.7
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071029; hg19: chr21-36422478; COSMIC: COSV55883511;