rs1200425

chr6-45559395-G-A

Variant summary

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

The XR_007059601.1(RUNX2-AS1):n.585-2237C>T 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 0.446 in 152,014 control chromosomes in the GnomAD database, including 15,987 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 0.45 (15987 hom., cov: 32)
• Consequence: RUNX2-AS1 XR_007059601.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.781

Genes affected

RUNX2-AS1 (HGNC:):

RUNX2 (HGNC:10472): (RUNX family transcription factor 2) This gene is a member of the RUNX family of transcription factors and encodes a nuclear protein with an Runt DNA-binding domain. This protein is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Two regions of potential trinucleotide repeat expansions are present in the N-terminal region of the encoded protein, and these and other mutations in this gene have been associated with the bone development disorder cleidocranial dysplasia (CCD). Transcript variants that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX2-AS1	XR_007059601.1	n.585-2237C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX2	ENST00000576263.5	c.1021+46988G>A		intron_variant		5
RUNX2	ENST00000478660.6	c.*178+45742G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67689 AN: 151896 Hom.: 15957 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.446 AC: 67766 AN: 152014 Hom.: 15987 Cov.: 32 AF XY: 0.444 AC XY: 33019 AN XY: 74298

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.399

Alfa AF: 0.389 Hom.: 16262

Bravo AF: 0.459

Asia WGS AF: 0.308 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.0
Dann	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1200425; hg19: chr6-45527132;