rs2636879

Positions:

• chr9-114282258-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032888.4(COL27A1):​c.3718-19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,607,638 control chromosomes in the GnomAD database, including 99,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8252 hom., cov: 33)
  • Exomes 𝑓: 0.35 (91434 hom.)
• Consequence: COL27A1 NM_032888.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.226

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 9-114282258-G-T is Benign according to our data. Variant chr9-114282258-G-T is described in ClinVar as [Benign]. Clinvar id is 1185236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL27A1	NM_032888.4	c.3718-19G>T		intron_variant		ENST00000356083.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL27A1	ENST00000356083.8	c.3718-19G>T		intron_variant		1	NM_032888.4	P1
COL27A1	ENST00000494090.6	c.*1155-19G>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49131 AN: 151958 Hom.: 8251 Cov.: 33

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.344

GnomAD3 exomes AF: 0.333 AC: 83467 AN: 250934 Hom.: 14316 AF XY: 0.330 AC XY: 44773 AN XY: 135694

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.383

Gnomad EAS exome AF: 0.352

Gnomad SAS exome AF: 0.223

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.351 AC: 511608 AN: 1455562 Hom.: 91434 Cov.: 32 AF XY: 0.348 AC XY: 252357 AN XY: 724558

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.365

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.323 AC: 49154 AN: 152076 Hom.: 8252 Cov.: 33 AF XY: 0.318 AC XY: 23607 AN XY: 74328

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.347

Alfa AF: 0.348 Hom.: 4893

Bravo AF: 0.328

Asia WGS AF: 0.319 AC: 1110 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Steel syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.51

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: rs2636879; hg19: chr9-117044538; COSMIC: COSV61923284;