21-35068403-T-A

Position:

• chr21-35068403-T-A

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-196-3331A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,174 control chromosomes in the GnomAD database, including 2,939 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 (2939 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 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.-196-3331A>T		intron_variant		5		ENSP00000477072

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29485 AN: 152056 Hom.: 2936 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.194 AC: 29515 AN: 152174 Hom.: 2939 Cov.: 32 AF XY: 0.195 AC XY: 14502 AN XY: 74386

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.195

Alfa AF: 0.105 Hom.: 161

Bravo AF: 0.197

Asia WGS AF: 0.239 AC: 831 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10483024; hg19: chr21-36440700;