rs753085

Variant names:

• chr9-114283167-G-A
• rs753085
• NM_032888.4:c.3880-542G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-114283167-G-A
• chr9-114283167-G-C

Variant summary

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

The NM_032888.4(COL27A1):​c.3880-542G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,154 control chromosomes in the GnomAD database, including 3,823 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 0.21 (3823 hom., cov: 33)
• Consequence: COL27A1 NM_032888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.909
• Publications: 3 publications found

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]

COL27A1 Gene-Disease associations (from GenCC):

• Steel syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032888.4. 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
	COL27A1	NM_032888.4	MANE Select	c.3880-542G>A		intron	N/A	NP_116277.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL27A1	ENST00000356083.8	TSL:1 MANE Select	c.3880-542G>A		intron	N/A	ENSP00000348385.3
	COL27A1	ENST00000494090.6	TSL:1	n.*1317-542G>A		intron	N/A	ENSP00000432928.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31189 AN: 152036 Hom.: 3825 Cov.: 33

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.205 AC: 31199 AN: 152154 Hom.: 3823 Cov.: 33 AF XY: 0.203 AC XY: 15065 AN XY: 74378

African (AFR) AF: 0.0717 AC: 2978 AN: 41546

American (AMR) AF: 0.252 AC: 3847 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1256 AN: 3468

East Asian (EAS) AF: 0.348 AC: 1787 AN: 5142

South Asian (SAS) AF: 0.158 AC: 762 AN: 4826

European-Finnish (FIN) AF: 0.213 AC: 2259 AN: 10592

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.258 AC: 17561 AN: 67990

Other (OTH) AF: 0.241 AC: 509 AN: 2112

Alfa AF: 0.232 Hom.: 942

Bravo AF: 0.206

Asia WGS AF: 0.279 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.74
DANN	Benign	0.47
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs753085; hg19: chr9-117045447;