Variant rs4143245 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032888.4(COL27A1):c.3570T>C(p.Leu1190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,609,222 control chromosomes in the GnomAD database, including 138,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13359 hom., cov: 33)

Exomes 𝑓: 0.41 ( 124774 hom. )

Consequence

COL27A1
NM_032888.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.974

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 9-114270742-T-C is Benign according to our data. Variant chr9-114270742-T-C is described in ClinVar as [Benign]. Clinvar id is 1165178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.974 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.474 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.3570T>C	p.Leu1190=	synonymous_variant	36/61	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.3570T>C	p.Leu1190=	synonymous_variant	36/61	1	NM_032888.4	ENSP00000348385	P1	Q8IZC6-1
COL27A1	ENST00000494090.6 linkuse as main transcript	c.*1007T>C		3_prime_UTR_variant, NMD_transcript_variant	33/58	1		ENSP00000432928
COL27A1	ENST00000477421.2 linkuse as main transcript	n.503T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62945

AN:

152000

Hom.:

13329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.413

GnomAD3 exomes

AF:

0.418

AC:

104248

AN:

249322

Hom.:

22803

AF XY:

0.412

AC XY:

55536

AN XY:

134864

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.541

Gnomad ASJ exome

AF:

0.344

Gnomad EAS exome

AF:

0.276

Gnomad SAS exome

AF:

0.348

Gnomad FIN exome

AF:

0.559

Gnomad NFE exome

AF:

0.408

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.410

AC:

597296

AN:

1457104

Hom.:

124774

Cov.:

AF XY:

0.408

AC XY:

295807

AN XY:

725044

show subpopulations

Gnomad4 AFR exome

AF:

0.381

Gnomad4 AMR exome

AF:

0.534

Gnomad4 ASJ exome

AF:

0.343

Gnomad4 EAS exome

AF:

0.414

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.552

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.399

GnomAD4 genome

AF:

0.414

AC:

63025

AN:

152118

Hom.:

13359

Cov.:

AF XY:

0.421

AC XY:

31341

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.388

Gnomad4 AMR

AF:

0.483

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.566

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.415

Alfa

AF:

0.403

Hom.:

20257

Bravo

AF:

0.406

Asia WGS

AF:

0.361

AC:

1255

AN:

3478

EpiCase

AF:

0.401

EpiControl

AF:

0.392

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

-0.87

CADD

Benign

0.82

DANN

Benign

0.42

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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