Genetic Variant COL11A1:c.1792-12_1792-10dupATG (chr1-103005900-C-CCAT) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_001854.4(COL11A1):c.1792-12_1792-10dupATG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.022 ( 100 hom., cov: 0)

Exomes 𝑓: 0.0057 ( 53 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:7

Conservation

PhyloP100: -0.166

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 -9 ACMG points.

BP6

Variant 1-103005900-C-CCAT is Benign according to our data. Variant chr1-103005900-C-CCAT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 166924.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Uncertain_significance=3}.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.1792-12_1792-10dupATG		intron_variant	Intron 17 of 66	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.1792-10_1792-9insATG		intron_variant	Intron 17 of 66	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3313

AN:

150378

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0699

Gnomad AMI

AF:

0.00332

Gnomad AMR

AF:

0.00885

Gnomad ASJ

AF:

0.00840

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00485

Gnomad FIN

AF:

0.00136

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00336

Gnomad OTH

AF:

0.0126

GnomAD3 exomes

AF:

0.00964

AC:

1882

AN:

195300

Hom.:

AF XY:

0.00837

AC XY:

880

AN XY:

105128

show subpopulations

Gnomad AFR exome

AF:

0.0755

Gnomad AMR exome

AF:

0.00471

Gnomad ASJ exome

AF:

0.00929

Gnomad EAS exome

AF:

0.0000809

Gnomad SAS exome

AF:

0.00669

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00470

Gnomad OTH exome

AF:

0.00657

GnomAD4 exome

AF:

0.00565

AC:

7732

AN:

1368102

Hom.:

Cov.:

AF XY:

0.00548

AC XY:

3736

AN XY:

681576

show subpopulations

Gnomad4 AFR exome

AF:

0.0711

Gnomad4 AMR exome

AF:

0.00422

Gnomad4 ASJ exome

AF:

0.00802

Gnomad4 EAS exome

AF:

0.0000547

Gnomad4 SAS exome

AF:

0.00565

Gnomad4 FIN exome

AF:

0.00115

Gnomad4 NFE exome

AF:

0.00391

Gnomad4 OTH exome

AF:

0.00791

GnomAD4 genome

AF:

0.0220

AC:

3318

AN:

150492

Hom.:

100

Cov.:

AF XY:

0.0215

AC XY:

1574

AN XY:

73358

show subpopulations

Gnomad4 AFR

AF:

0.0698

Gnomad4 AMR

AF:

0.00883

Gnomad4 ASJ

AF:

0.00840

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00486

Gnomad4 FIN

AF:

0.00136

Gnomad4 NFE

AF:

0.00337

Gnomad4 OTH

AF:

0.0125

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:4

Feb 28, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 24, 2014

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Marshall syndrome

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibrochondrogenesis 1

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Stickler Syndrome, Dominant

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Connective tissue disorder

Benign:1

Mar 01, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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