rs1928529

Variant names:

• chr6-45566428-C-T
• rs1928529
• ENST00000576263.5:c.1021+54021C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000576263.5(RUNX2):​c.1021+54021C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,994 control chromosomes in the GnomAD database, including 10,044 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 0.35 (10044 hom., cov: 32)
• Consequence: RUNX2 ENST00000576263.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 2 publications found

Genes affected

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]

RUNX2-AS1 (HGNC:53512): (RUNX2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000576263.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX2-AS1	NR_187177.1		n.1784-30G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX2	ENST00000576263.5	TSL:5	c.1021+54021C>T		intron	N/A	ENSP00000458178.1
	RUNX2	ENST00000478660.6	TSL:5	n.*178+52775C>T		intron	N/A	ENSP00000460188.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52766 AN: 151876 Hom.: 10028 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.348 AC: 52829 AN: 151994 Hom.: 10044 Cov.: 32 AF XY: 0.344 AC XY: 25554 AN XY: 74296

African (AFR) AF: 0.499 AC: 20695 AN: 41438

American (AMR) AF: 0.363 AC: 5538 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1176 AN: 5166

South Asian (SAS) AF: 0.184 AC: 883 AN: 4810

European-Finnish (FIN) AF: 0.278 AC: 2934 AN: 10554

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19554 AN: 67964

Other (OTH) AF: 0.353 AC: 746 AN: 2114

Alfa AF: 0.305 Hom.: 12407

Bravo AF: 0.360

Asia WGS AF: 0.228 AC: 795 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.56
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1928529; hg19: chr6-45534165;