rs1490740

Variant names:

• chr9-114269981-C-T
• rs1490740
• NM_032888.4:c.3555+687C>T

Variant summary

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

The NM_032888.4(COL27A1):​c.3555+687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,044 control chromosomes in the GnomAD database, including 2,837 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 0.18 (2837 hom., cov: 33)
• Consequence: COL27A1 NM_032888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL27A1	NM_032888.4	c.3555+687C>T		intron_variant	Intron 35 of 60	ENST00000356083.8	NP_116277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL27A1	ENST00000356083.8	c.3555+687C>T		intron_variant	Intron 35 of 60	1	NM_032888.4	ENSP00000348385.3
COL27A1	ENST00000494090.6	n.*992+687C>T		intron_variant	Intron 32 of 57	1		ENSP00000432928.1
COL27A1	ENST00000477421.2	n.488+687C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27640 AN: 151926 Hom.: 2834 Cov.: 33

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0923

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.182 AC: 27657 AN: 152044 Hom.: 2837 Cov.: 33 AF XY: 0.179 AC XY: 13278 AN XY: 74326

African (AFR) AF: 0.266 AC: 11010 AN: 41462

American (AMR) AF: 0.124 AC: 1902 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0923 AC: 320 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.0830 AC: 400 AN: 4822

European-Finnish (FIN) AF: 0.179 AC: 1887 AN: 10562

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11584 AN: 67948

Other (OTH) AF: 0.148 AC: 311 AN: 2106

Alfa AF: 0.166 Hom.: 3644

Bravo AF: 0.181

Asia WGS AF: 0.0470 AC: 164 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	7.5
DANN	Benign	0.73
PhyloP100		0.026
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1490740; hg19: chr9-117032261;