rs3767272

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+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,453,522 control chromosomes in the GnomAD database, including 734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 61 hom., cov: 32)

Exomes 𝑓: 0.028 ( 673 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0650

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=-0.89).

BP6

Variant 1-103017773-T-C is Benign according to our data. Variant chr1-103017773-T-C is described in ClinVar as Benign. ClinVar VariationId is 674969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.1413+47A>G		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+47A>G		intron_variant	Intron 11 of 66	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3671

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0274

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.0668

Gnomad SAS

AF:

0.0534

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0291

GnomAD2 exomes

AF:

0.0299

AC:

7509

AN:

250830

AF XY:

0.0321

show subpopulations

Gnomad AFR exome

AF:

0.0128

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.0435

Gnomad EAS exome

AF:

0.0750

Gnomad FIN exome

AF:

0.00315

Gnomad NFE exome

AF:

0.0284

Gnomad OTH exome

AF:

0.0285

GnomAD4 exome

AF:

0.0284

AC:

36981

AN:

1301304

Hom.:

673

Cov.:

AF XY:

0.0293

AC XY:

19242

AN XY:

656534

show subpopulations

African (AFR)

AF:

0.0140

AC:

425

AN:

30378

American (AMR)

AF:

0.0166

AC:

737

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.0429

AC:

1082

AN:

25206

East Asian (EAS)

AF:

0.0606

AC:

2359

AN:

38948

South Asian (SAS)

AF:

0.0484

AC:

4022

AN:

83078

European-Finnish (FIN)

AF:

0.00422

AC:

225

AN:

53294

Middle Eastern (MID)

AF:

0.0419

AC:

219

AN:

5230

European-Non Finnish (NFE)

AF:

0.0272

AC:

26281

AN:

965716

Other (OTH)

AF:

0.0297

AC:

1631

AN:

54958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1894

3788

5681

7575

9469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

976

1952

2928

3904

4880

<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:

0.0242

AC:

3683

AN:

152218

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

1790

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0145

AC:

602

AN:

41550

American (AMR)

AF:

0.0274

AC:

418

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3470

East Asian (EAS)

AF:

0.0669

AC:

347

AN:

5186

South Asian (SAS)

AF:

0.0536

AC:

259

AN:

4828

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0263

AC:

1790

AN:

67996

Other (OTH)

AF:

0.0293

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

178

357

535

714

892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0255

Hom.:

Bravo

AF:

0.0252

Asia WGS

AF:

0.0440

AC:

151

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.6

(source)

DANN

Benign

0.32

PhyloP100

0.065

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