rs999599

Positions:

• chr9-114249315-C-T

Variant summary

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

The ENST00000356083.8(COL27A1):​c.2980-1300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,112 control chromosomes in the GnomAD database, including 8,270 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 0.32 (8270 hom., cov: 33)
• Consequence: COL27A1 ENST00000356083.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426

Genes affected

COL27A1 (HGNC:22986): (collagen type XXVII alpha 1 chain) This gene encodes a member of the fibrillar collagen family, and plays a role during the calcification of cartilage and the transition of cartilage to bone. The encoded protein product is a preproprotein. It includes an N-terminal signal peptide, which is followed by an N-terminal propetide, mature peptide and a C-terminal propeptide. The N-terminal propeptide contains thrombospondin N-terminal-like and laminin G-like domains. The mature peptide is a major triple-helical region. The C-terminal propeptide, also known as COLFI domain, plays crucial roles in tissue growth and repair. Mutations in this gene cause Steel syndrome. Alternatively spliced transcript variants have been found, but the full-length nature of some variants has not been determined. [provided by RefSeq, Sep 2014]

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 (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL27A1	NM_032888.4	c.2980-1300C>T		intron_variant		ENST00000356083.8	NP_116277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL27A1	ENST00000356083.8	c.2980-1300C>T		intron_variant		1	NM_032888.4	ENSP00000348385	P1
COL27A1	ENST00000494090.6	c.*410-1300C>T		intron_variant, NMD_transcript_variant		1		ENSP00000432928

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49395 AN: 151992 Hom.: 8266 Cov.: 33

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.325 AC: 49398 AN: 152112 Hom.: 8270 Cov.: 33 AF XY: 0.325 AC XY: 24187 AN XY: 74366

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.309

Alfa AF: 0.356 Hom.: 20830

Bravo AF: 0.310

Asia WGS AF: 0.306 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs999599; hg19: chr9-117011595;