rs6668897

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.488+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,598,358 control chromosomes in the GnomAD database, including 19,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1596 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17973 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0880

Publications

3 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=-0.77).

BP6

Variant 1-103078635-C-T is Benign according to our data. Variant chr1-103078635-C-T is described in ClinVar as [Benign]. Clinvar id is 258471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.488+23G>A		intron_variant	Intron 3 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.488+23G>A		intron_variant	Intron 3 of 66	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20913

AN:

151816

Hom.:

1594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.0769

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.00890

Gnomad SAS

AF:

0.0908

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.127

GnomAD2 exomes

AF:

0.149

AC:

37255

AN:

250088

AF XY:

0.147

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.143

Gnomad EAS exome

AF:

0.00631

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.153

AC:

221820

AN:

1446424

Hom.:

17973

Cov.:

AF XY:

0.152

AC XY:

109760

AN XY:

720688

show subpopulations

African (AFR)

AF:

0.106

AC:

3514

AN:

33110

American (AMR)

AF:

0.211

AC:

9388

AN:

44490

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3683

AN:

26004

East Asian (EAS)

AF:

0.00692

AC:

274

AN:

39578

South Asian (SAS)

AF:

0.102

AC:

8793

AN:

85922

European-Finnish (FIN)

AF:

0.207

AC:

11021

AN:

53320

Middle Eastern (MID)

AF:

0.185

AC:

1062

AN:

5734

European-Non Finnish (NFE)

AF:

0.159

AC:

175050

AN:

1098410

Other (OTH)

AF:

0.151

AC:

9035

AN:

59856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

8742

17484

26225

34967

43709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6078

12156

18234

24312

30390

<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:

0.138

AC:

20936

AN:

151934

Hom.:

1596

Cov.:

AF XY:

0.138

AC XY:

10280

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.102

AC:

4248

AN:

41464

American (AMR)

AF:

0.153

AC:

2337

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

483

AN:

3470

East Asian (EAS)

AF:

0.00892

AC:

AN:

5158

South Asian (SAS)

AF:

0.0909

AC:

437

AN:

4810

European-Finnish (FIN)

AF:

0.207

AC:

2177

AN:

10540

Middle Eastern (MID)

AF:

0.147

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.159

AC:

10829

AN:

67926

Other (OTH)

AF:

0.126

AC:

266

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

888

1775

2663

3550

4438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.156

Hom.:

503

Bravo

AF:

0.134

Asia WGS

AF:

0.0590

AC:

204

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 26, 2018

GeneDx

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.77

CADD

Benign

5.9

(source)

DANN

Benign

0.71

PhyloP100

-0.088

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