9-114228704-C-G

Position:

• chr9-114228704-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
COL27A1	NM_032888.4	c.2467-2375C>G		intron_variant		ENST00000356083.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL27A1	ENST00000356083.8	c.2467-2375C>G		intron_variant		1	NM_032888.4	P1
COL27A1	ENST00000494090.6	c.1361-2375C>G		intron_variant, NMD_transcript_variant		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

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.724

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4979356; hg19: chr9-116990984;