Variant 9-114210993-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_032888.4(COL27A1):c.2334C>T(p.Gly778Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,613,340 control chromosomes in the GnomAD database, including 5,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 675 hom., cov: 33)

Exomes 𝑓: 0.075 ( 4471 hom. )

Consequence

COL27A1
NM_032888.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.263

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:

COL27A1 (HGNC:):

COL27A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 9-114210993-C-T is Benign according to our data. Variant chr9-114210993-C-T is described in ClinVar as [Benign]. Clinvar id is 1167368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.263 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 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.2334C>T	p.Gly778Gly	synonymous_variant	12/61	ENST00000356083.8	NP_116277.2	Q8IZC6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL27A1	ENST00000356083.8 linkuse as main transcript	c.2334C>T	p.Gly778Gly	synonymous_variant	12/61	1	NM_032888.4	ENSP00000348385.3	Q8IZC6-1
COL27A1	ENST00000451716.5 linkuse as main transcript	c.2022C>T	p.Gly674Gly	synonymous_variant	7/8	1		ENSP00000391328.1	Q5T1U7
COL27A1	ENST00000494090.6 linkuse as main transcript	n.1227C>T		non_coding_transcript_exon_variant	9/58	1		ENSP00000432928.1	H0YD40

Frequencies

GnomAD3 genomes

AF:

0.0878

AC:

13364

AN:

152170

Hom.:

674

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0710

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.0528

Gnomad SAS

AF:

0.0576

Gnomad FIN

AF:

0.0335

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0789

Gnomad OTH

AF:

0.0967

GnomAD3 exomes

AF:

0.0731

AC:

18385

AN:

251404

Hom.:

801

AF XY:

0.0733

AC XY:

9962

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.0517

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.0464

Gnomad SAS exome

AF:

0.0609

Gnomad FIN exome

AF:

0.0367

Gnomad NFE exome

AF:

0.0792

Gnomad OTH exome

AF:

0.0854

GnomAD4 exome

AF:

0.0747

AC:

109077

AN:

1461052

Hom.:

4471

Cov.:

AF XY:

0.0748

AC XY:

54382

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.0535

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.0522

Gnomad4 SAS exome

AF:

0.0605

Gnomad4 FIN exome

AF:

0.0355

Gnomad4 NFE exome

AF:

0.0752

Gnomad4 OTH exome

AF:

0.0816

GnomAD4 genome

AF:

0.0878

AC:

13372

AN:

152288

Hom.:

675

Cov.:

AF XY:

0.0850

AC XY:

6331

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.0708

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.0525

Gnomad4 SAS

AF:

0.0568

Gnomad4 FIN

AF:

0.0335

Gnomad4 NFE

AF:

0.0788

Gnomad4 OTH

AF:

0.0967

Alfa

AF:

0.0783

Hom.:

335

Bravo

AF:

0.0919

Asia WGS

AF:

0.0710

AC:

247

AN:

3478

EpiCase

AF:

0.0823

EpiControl

AF:

0.0870

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

4.8

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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