Variant rs2636879 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.226

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
COL27A1	NM_032888.4 linkuse as main transcript	c.3718-19G>T		intron_variant		ENST00000356083.8	NP_116277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL27A1	ENST00000356083.8 linkuse as main transcript	c.3718-19G>T		intron_variant		1	NM_032888.4	ENSP00000348385	P1	Q8IZC6-1
COL27A1	ENST00000494090.6 linkuse as main transcript	c.*1155-19G>T		intron_variant, NMD_transcript_variant		1		ENSP00000432928

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49131

AN:

151958

Hom.:

8251

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.348

AC XY:

252357

AN XY:

724558

show subpopulations

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.:

AF XY:

0.318

AC XY:

23607

AN XY:

74328

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over