rs28648038

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.3978+38T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,484,264 control chromosomes in the GnomAD database, including 10,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 743 hom., cov: 32)

Exomes 𝑓: 0.12 ( 9944 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.471

Publications

4 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=-0.88).

BP6

Variant 1-102914314-A-C is Benign according to our data. Variant chr1-102914314-A-C is described in ClinVar as Benign. ClinVar VariationId is 258462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.3978+38T>G		intron_variant	Intron 52 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.3978+38T>G		intron_variant	Intron 52 of 66	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.0919

AC:

13950

AN:

151878

Hom.:

740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0569

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0725

Gnomad ASJ

AF:

0.0646

Gnomad EAS

AF:

0.0147

Gnomad SAS

AF:

0.0526

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.0980

GnomAD2 exomes

AF:

0.0941

AC:

22618

AN:

240412

AF XY:

0.0948

show subpopulations

Gnomad AFR exome

AF:

0.0548

Gnomad AMR exome

AF:

0.0653

Gnomad ASJ exome

AF:

0.0724

Gnomad EAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.0984

GnomAD4 exome

AF:

0.117

AC:

156201

AN:

1332268

Hom.:

9944

Cov.:

AF XY:

0.115

AC XY:

76974

AN XY:

668574

show subpopulations

African (AFR)

AF:

0.0540

AC:

1724

AN:

31922

American (AMR)

AF:

0.0672

AC:

2937

AN:

43692

Ashkenazi Jewish (ASJ)

AF:

0.0742

AC:

1869

AN:

25200

East Asian (EAS)

AF:

0.0124

AC:

481

AN:

38832

South Asian (SAS)

AF:

0.0596

AC:

4835

AN:

81084

European-Finnish (FIN)

AF:

0.138

AC:

7282

AN:

52608

Middle Eastern (MID)

AF:

0.113

AC:

628

AN:

5568

European-Non Finnish (NFE)

AF:

0.131

AC:

130521

AN:

997326

Other (OTH)

AF:

0.106

AC:

5924

AN:

56036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

6462

12923

19385

25846

32308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4538

9076

13614

18152

22690

<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:

0.0919

AC:

13965

AN:

151996

Hom.:

743

Cov.:

AF XY:

0.0922

AC XY:

6847

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.0570

AC:

2362

AN:

41466

American (AMR)

AF:

0.0724

AC:

1106

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0646

AC:

224

AN:

3470

East Asian (EAS)

AF:

0.0149

AC:

AN:

5164

South Asian (SAS)

AF:

0.0532

AC:

256

AN:

4810

European-Finnish (FIN)

AF:

0.147

AC:

1554

AN:

10546

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

8051

AN:

67962

Other (OTH)

AF:

0.0979

AC:

206

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

644

1288

1931

2575

3219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.105

Hom.:

261

Bravo

AF:

0.0877

Asia WGS

AF:

0.0640

AC:

223

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 23, 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

-0.88

CADD

Benign

0.20

(source)

DANN

Benign

0.45

PhyloP100

-0.47

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