rs1012282

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001854.4(COL11A1):c.3168+41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,571,308 control chromosomes in the GnomAD database, including 55,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6451 hom., cov: 32)

Exomes 𝑓: 0.26 ( 48932 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.49

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

Marshall syndrome
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
Stickler syndrome type 2
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Orphanet, Genomics England PanelApp
fibrochondrogenesis 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal dominant 37
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
fibrochondrogenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive Stickler syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COL11A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-102961825-A-G is Benign according to our data. Variant chr1-102961825-A-G is described in ClinVar as Benign. ClinVar VariationId is 258456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.3168+41T>C		intron_variant	Intron 41 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.3168+41T>C		intron_variant	Intron 41 of 66	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43023

AN:

152016

Hom.:

6440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.0864

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.261

GnomAD2 exomes

AF:

0.248

AC:

60776

AN:

244704

AF XY:

0.243

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.0884

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.258

AC:

365859

AN:

1419174

Hom.:

48932

Cov.:

AF XY:

0.255

AC XY:

180607

AN XY:

708108

show subpopulations

African (AFR)

AF:

0.386

AC:

12652

AN:

32752

American (AMR)

AF:

0.272

AC:

11972

AN:

44080

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

5927

AN:

25732

East Asian (EAS)

AF:

0.0745

AC:

2945

AN:

39512

South Asian (SAS)

AF:

0.168

AC:

14180

AN:

84574

European-Finnish (FIN)

AF:

0.271

AC:

14398

AN:

53052

Middle Eastern (MID)

AF:

0.292

AC:

1656

AN:

5672

European-Non Finnish (NFE)

AF:

0.267

AC:

286961

AN:

1074876

Other (OTH)

AF:

0.257

AC:

15168

AN:

58924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

12487

24975

37462

49950

62437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9436

18872

28308

37744

47180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.283

AC:

43081

AN:

152134

Hom.:

6451

Cov.:

AF XY:

0.280

AC XY:

20829

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.381

AC:

15803

AN:

41502

American (AMR)

AF:

0.250

AC:

3821

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

769

AN:

3472

East Asian (EAS)

AF:

0.0864

AC:

447

AN:

5172

South Asian (SAS)

AF:

0.162

AC:

782

AN:

4832

European-Finnish (FIN)

AF:

0.271

AC:

2868

AN:

10602

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17848

AN:

67978

Other (OTH)

AF:

0.260

AC:

548

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1541

3081

4622

6162

7703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.276

Hom.:

10822

Bravo

AF:

0.288

Asia WGS

AF:

0.166

AC:

576

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

- -

Fibrochondrogenesis 1

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Stickler syndrome type 2

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

-0.91

CADD

Benign

1.2

(source)

DANN

Benign

0.36

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over