9-114287611-T-G

Variant names:

• chr9-114287611-T-G
• rs946053
• NM_032888.4:c.3988-844T>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.3988-844T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,026 control chromosomes in the GnomAD database, including 31,741 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 0.63 (31741 hom., cov: 32)
• Consequence: COL27A1 NM_032888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 22 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)

LOC124902252 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL27A1	NM_032888.4	c.3988-844T>G		intron_variant	Intron 41 of 60	ENST00000356083.8	NP_116277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL27A1	ENST00000356083.8	c.3988-844T>G		intron_variant	Intron 41 of 60	1	NM_032888.4	ENSP00000348385.3
COL27A1	ENST00000494090.6	n.*1425-844T>G		intron_variant	Intron 38 of 57	1		ENSP00000432928.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95592 AN: 151908 Hom.: 31689 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.630 AC: 95704 AN: 152026 Hom.: 31741 Cov.: 32 AF XY: 0.630 AC XY: 46787 AN XY: 74316

African (AFR) AF: 0.791 AC: 32818 AN: 41468

American (AMR) AF: 0.702 AC: 10735 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2218 AN: 3466

East Asian (EAS) AF: 0.933 AC: 4804 AN: 5150

South Asian (SAS) AF: 0.746 AC: 3588 AN: 4810

European-Finnish (FIN) AF: 0.413 AC: 4368 AN: 10574

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35076 AN: 67958

Other (OTH) AF: 0.636 AC: 1343 AN: 2112

Alfa AF: 0.566 Hom.: 86589

Bravo AF: 0.662

Asia WGS AF: 0.857 AC: 2979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.087
DANN	Benign	0.34
PhyloP100		-1.6
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: rs946053; hg19: chr9-117049891;