rs485817

chr6-45555675-A-G

Variant summary

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

The XR_007059601.1(RUNX2-AS1):n.2068T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,556 control chromosomes in the GnomAD database, including 18,122 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 0.49 (18122 hom., cov: 30)
• Consequence: RUNX2-AS1 XR_007059601.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX2-AS1	XR_007059601.1	n.2068T>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX2	ENST00000576263.5	c.1021+43268A>G		intron_variant		5
RUNX2	ENST00000478660.6	c.*178+42022A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.488 AC: 73873 AN: 151438 Hom.: 18124 Cov.: 30

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.488 AC: 73890 AN: 151556 Hom.: 18122 Cov.: 30 AF XY: 0.481 AC XY: 35619 AN XY: 74072

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.479

Alfa AF: 0.511 Hom.: 28068

Bravo AF: 0.487

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.13
Dann	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs485817; hg19: chr6-45523412;