rs2622867

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2295+37A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 1,612,872 control chromosomes in the GnomAD database, including 743,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64681 hom., cov: 33)

Exomes 𝑓: 0.96 ( 678759 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.599

Publications

13 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=-0.8).

BP6

Variant 1-102995952-T-A is Benign according to our data. Variant chr1-102995952-T-A is described in ClinVar as Benign. ClinVar VariationId is 258443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.2295+37A>T		intron_variant	Intron 27 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.2295+37A>T		intron_variant	Intron 27 of 66	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.919

AC:

139762

AN:

152146

Hom.:

64633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.800

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.953

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.986

Gnomad FIN

AF:

0.969

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.964

Gnomad OTH

AF:

0.910

GnomAD2 exomes

AF:

0.956

AC:

240007

AN:

250946

AF XY:

0.961

show subpopulations

Gnomad AFR exome

AF:

0.791

Gnomad AMR exome

AF:

0.972

Gnomad ASJ exome

AF:

0.896

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.970

Gnomad NFE exome

AF:

0.963

Gnomad OTH exome

AF:

0.951

GnomAD4 exome

AF:

0.964

AC:

1407358

AN:

1460608

Hom.:

678759

Cov.:

AF XY:

0.965

AC XY:

701033

AN XY:

726654

show subpopulations

African (AFR)

AF:

0.787

AC:

26316

AN:

33424

American (AMR)

AF:

0.969

AC:

43240

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.896

AC:

23391

AN:

26106

East Asian (EAS)

AF:

1.00

AC:

39637

AN:

39638

South Asian (SAS)

AF:

0.987

AC:

85070

AN:

86222

European-Finnish (FIN)

AF:

0.970

AC:

51782

AN:

53400

Middle Eastern (MID)

AF:

0.941

AC:

5294

AN:

5626

European-Non Finnish (NFE)

AF:

0.967

AC:

1075097

AN:

1111220

Other (OTH)

AF:

0.954

AC:

57531

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

2874

5748

8623

11497

14371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21618

43236

64854

86472

108090

<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:

0.919

AC:

139868

AN:

152264

Hom.:

64681

Cov.:

AF XY:

0.922

AC XY:

68624

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.800

AC:

33219

AN:

41528

American (AMR)

AF:

0.953

AC:

14567

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

3139

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5184

AN:

5184

South Asian (SAS)

AF:

0.986

AC:

4759

AN:

4828

European-Finnish (FIN)

AF:

0.969

AC:

10293

AN:

10620

Middle Eastern (MID)

AF:

0.942

AC:

277

AN:

294

European-Non Finnish (NFE)

AF:

0.964

AC:

65594

AN:

68026

Other (OTH)

AF:

0.911

AC:

1925

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

557

1113

1670

2226

2783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.937

Hom.:

12325

Bravo

AF:

0.912

Asia WGS

AF:

0.983

AC:

3414

AN:

3476

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 14, 2018

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. -

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

-0.80

CADD

Benign

0.39

(source)

DANN

Benign

0.52

PhyloP100

-0.60

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