9-114228704-C-G

Variant names:

• chr9-114228704-C-G
• rs4979356
• NM_032888.4:c.2467-2375C>G

Variant summary

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

The NM_032888.4(COL27A1):​c.2467-2375C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,134 control chromosomes in the GnomAD database, including 39,467 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 0.70 (39467 hom., cov: 34)
• Consequence: COL27A1 NM_032888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL27A1	NM_032888.4	c.2467-2375C>G		intron_variant	Intron 14 of 60	ENST00000356083.8	NP_116277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL27A1	ENST00000356083.8	c.2467-2375C>G		intron_variant	Intron 14 of 60	1	NM_032888.4	ENSP00000348385.3
COL27A1	ENST00000494090.6	n.1360-2375C>G		intron_variant	Intron 11 of 57	1		ENSP00000432928.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106720 AN: 152016 Hom.: 39435 Cov.: 34

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.702 AC: 106804 AN: 152134 Hom.: 39467 Cov.: 34 AF XY: 0.700 AC XY: 52016 AN XY: 74352

African (AFR) AF: 0.466 AC: 19348 AN: 41492

American (AMR) AF: 0.774 AC: 11833 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2508 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2267 AN: 5170

South Asian (SAS) AF: 0.888 AC: 4282 AN: 4822

European-Finnish (FIN) AF: 0.723 AC: 7638 AN: 10568

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56393 AN: 68002

Other (OTH) AF: 0.724 AC: 1530 AN: 2112

Alfa AF: 0.704 Hom.: 2583

Bravo AF: 0.686

Asia WGS AF: 0.678 AC: 2357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.019
DANN	Benign	0.42
PhyloP100		-1.1
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: rs4979356; hg19: chr9-116990984;