NM_001854.4:c.4770T>C

Variant names:

Variant summary

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

The NM_001854.4(COL11A1):c.4770T>C(p.Ile1590Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,613,456 control chromosomes in the GnomAD database, including 289,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 21765 hom., cov: 31)

Exomes 𝑓: 0.60 ( 267716 hom. )

Consequence

COL11A1
NM_001854.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.790

Variant links:

Genes affected

COL11A1 (HGNC:2186): (collagen type XI alpha 1 chain) This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Mutations in this gene are associated with type II Stickler syndrome and with Marshall syndrome. A single-nucleotide polymorphism in this gene is also associated with susceptibility to lumbar disc herniation. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]

COL11A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-102886895-A-G is Benign according to our data. Variant chr1-102886895-A-G is described in ClinVar as [Benign]. Clinvar id is 258470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-102886895-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.4770T>C	p.Ile1590Ile	synonymous_variant	Exon 63 of 67	ENST00000370096.9	NP_001845.3	P12107-1Q59HB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9 link	c.4770T>C	p.Ile1590Ile	synonymous_variant	Exon 63 of 67	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74268

AN:

151790

Hom.:

21753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.637

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.665

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.639

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.617

Gnomad OTH

AF:

0.521

GnomAD3 exomes

AF:

0.593

AC:

149024

AN:

251204

Hom.:

46721

AF XY:

0.596

AC XY:

80956

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.734

Gnomad ASJ exome

AF:

0.556

Gnomad EAS exome

AF:

0.638

Gnomad SAS exome

AF:

0.571

Gnomad FIN exome

AF:

0.648

Gnomad NFE exome

AF:

0.609

Gnomad OTH exome

AF:

0.611

GnomAD4 exome

AF:

0.600

AC:

876350

AN:

1461548

Hom.:

267716

Cov.:

AF XY:

0.600

AC XY:

436366

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.724

Gnomad4 ASJ exome

AF:

0.556

Gnomad4 EAS exome

AF:

0.630

Gnomad4 SAS exome

AF:

0.573

Gnomad4 FIN exome

AF:

0.649

Gnomad4 NFE exome

AF:

0.610

Gnomad4 OTH exome

AF:

0.584

GnomAD4 genome

AF:

0.489

AC:

74287

AN:

151908

Hom.:

21765

Cov.:

AF XY:

0.496

AC XY:

36817

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.657

Gnomad4 ASJ

AF:

0.564

Gnomad4 EAS

AF:

0.665

Gnomad4 SAS

AF:

0.569

Gnomad4 FIN

AF:

0.639

Gnomad4 NFE

AF:

0.617

Gnomad4 OTH

AF:

0.525

Alfa

AF:

0.584

Hom.:

43409

Bravo

AF:

0.477

Asia WGS

AF:

0.591

AC:

2050

AN:

3476

EpiCase

AF:

0.605

EpiControl

AF:

0.604

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 29, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Fibrochondrogenesis 1

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Stickler syndrome type 2

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hearing loss, autosomal dominant 37

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Marshall syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.24

DANN

Benign

0.68

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