9-114228715-T-C

Variant names:

• chr9-114228715-T-C
• rs4979357
• NM_032888.4:c.2467-2364T>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.2467-2364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,164 control chromosomes in the GnomAD database, including 39,523 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 (39523 hom., cov: 34)
• Consequence: COL27A1 NM_032888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15
• Publications: 4 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 = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL27A1	NM_032888.4	c.2467-2364T>C		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.2467-2364T>C		intron_variant	Intron 14 of 60	1	NM_032888.4	ENSP00000348385.3
COL27A1	ENST00000494090.6	n.1360-2364T>C		intron_variant	Intron 11 of 57	1		ENSP00000432928.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106828 AN: 152046 Hom.: 39489 Cov.: 34

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.703 AC: 106915 AN: 152164 Hom.: 39523 Cov.: 34 AF XY: 0.700 AC XY: 52075 AN XY: 74382

African (AFR) AF: 0.468 AC: 19442 AN: 41504

American (AMR) AF: 0.773 AC: 11819 AN: 15286

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

East Asian (EAS) AF: 0.440 AC: 2279 AN: 5180

South Asian (SAS) AF: 0.889 AC: 4289 AN: 4826

European-Finnish (FIN) AF: 0.722 AC: 7648 AN: 10586

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.829 AC: 56390 AN: 67990

Other (OTH) AF: 0.725 AC: 1532 AN: 2114

Alfa AF: 0.793 Hom.: 76979

Bravo AF: 0.687

Asia WGS AF: 0.680 AC: 2363 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	0.063
DANN	Benign	0.48
PhyloP100		-3.1
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: rs4979357; hg19: chr9-116990995;