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.

1-103005900-CCATCATCATCATCATCAT-CCATCATCATCATCATCATCAT

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