NM_032888.4:c.2467-2288G>A

Variant names:

• chr9-114228791-G-A
• rs7868992
• NM_032888.4:c.2467-2288G>A

Variant summary

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

The NM_032888.4(COL27A1):​c.2467-2288G>A 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 152,000 control chromosomes in the GnomAD database, including 31,205 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 (31205 hom., cov: 31)
• Consequence: COL27A1 NM_032888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992
• Publications: 23 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.804 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.2467-2288G>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.2467-2288G>A		intron	N/A	ENSP00000348385.3
	COL27A1	ENST00000494090.6	TSL:1	n.1360-2288G>A		intron	N/A	ENSP00000432928.1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95726 AN: 151882 Hom.: 31183 Cov.: 31

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.630 AC: 95786 AN: 152000 Hom.: 31205 Cov.: 31 AF XY: 0.630 AC XY: 46786 AN XY: 74284

African (AFR) AF: 0.482 AC: 19954 AN: 41434

American (AMR) AF: 0.663 AC: 10132 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2220 AN: 3466

East Asian (EAS) AF: 0.329 AC: 1700 AN: 5164

South Asian (SAS) AF: 0.826 AC: 3978 AN: 4818

European-Finnish (FIN) AF: 0.662 AC: 6977 AN: 10538

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48745 AN: 67992

Other (OTH) AF: 0.637 AC: 1346 AN: 2112

Alfa AF: 0.680 Hom.: 113644

Bravo AF: 0.615

Asia WGS AF: 0.593 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.77
PhyloP100		-0.99
Mutation Taster		=99/1	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: rs7868992; hg19: chr9-116991071;