rs445984

Positions:

• chr21-35525560-A-G
• chr21-35525560-A-C

Variant summary

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

The NR_073512.1(LOC100506403):​n.105+55100T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,986 control chromosomes in the GnomAD database, including 11,811 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 0.39 (11811 hom., cov: 31)
• Consequence: LOC100506403 NR_073512.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31

Genes affected

LOC100506403 (HGNC:):

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100506403	NR_073512.1	n.105+55100T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000475045.6	c.-262+55100T>C		intron_variant		5		ENSP00000477072
RUNX1	ENST00000467692.5	n.101+55100T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58864 AN: 151868 Hom.: 11787 Cov.: 31

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.388 AC: 58933 AN: 151986 Hom.: 11811 Cov.: 31 AF XY: 0.386 AC XY: 28652 AN XY: 74280

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.410

Alfa AF: 0.389 Hom.: 1953

Bravo AF: 0.385

Asia WGS AF: 0.248 AC: 861 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	0.20
DANN	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs445984; hg19: chr21-36897858;