1-103017802-T-A

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.1413+18A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 1,596,772 control chromosomes in the GnomAD database, including 3,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 219 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2830 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.50

Publications

7 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=-0.9).

BP6

Variant 1-103017802-T-A is Benign according to our data. Variant chr1-103017802-T-A is described in ClinVar as Benign. ClinVar VariationId is 258439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.1413+18A>T		intron_variant	Intron 11 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.1413+18A>T		intron_variant	Intron 11 of 66	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6220

AN:

152082

Hom.:

218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0730

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0577

Gnomad OTH

AF:

0.0244

GnomAD2 exomes

AF:

0.0547

AC:

13751

AN:

251190

AF XY:

0.0507

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.0534

Gnomad NFE exome

AF:

0.0561

Gnomad OTH exome

AF:

0.0467

GnomAD4 exome

AF:

0.0562

AC:

81198

AN:

1444572

Hom.:

2830

Cov.:

AF XY:

0.0550

AC XY:

39600

AN XY:

719804

show subpopulations

African (AFR)

AF:

0.00880

AC:

292

AN:

33174

American (AMR)

AF:

0.135

AC:

6046

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

278

AN:

26016

East Asian (EAS)

AF:

0.00227

AC:

AN:

39618

South Asian (SAS)

AF:

0.0239

AC:

2051

AN:

85956

European-Finnish (FIN)

AF:

0.0570

AC:

3043

AN:

53400

Middle Eastern (MID)

AF:

0.0125

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.0605

AC:

66318

AN:

1096238

Other (OTH)

AF:

0.0503

AC:

3009

AN:

59784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

3172

6344

9517

12689

15861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2448

4896

7344

9792

12240

<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:

0.0409

AC:

6221

AN:

152200

Hom.:

219

Cov.:

AF XY:

0.0406

AC XY:

3019

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0108

AC:

450

AN:

41548

American (AMR)

AF:

0.0731

AC:

1116

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3472

East Asian (EAS)

AF:

0.00290

AC:

AN:

5172

South Asian (SAS)

AF:

0.0205

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0488

AC:

518

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0577

AC:

3924

AN:

68000

Other (OTH)

AF:

0.0241

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

283

565

848

1130

1413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0464

Hom.:

Bravo

AF:

0.0423

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 11, 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. -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.52

(source)

DANN

Benign

0.46

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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