chr1-102961851-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001854.4(COL11A1):c.3168+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0666 in 1,606,974 control chromosomes in the GnomAD database, including 4,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 269 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3760 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.25

Publications

11 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 1-102961851-T-C is Benign according to our data. Variant chr1-102961851-T-C is described in ClinVar as Benign. ClinVar VariationId is 258455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001854.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COL11A1	NM_001854.4	MANE Select	c.3168+15A>G	intron	N/A	NP_001845.3
COL11A1	NM_080629.3		c.3204+15A>G	intron	N/A	NP_542196.2
COL11A1	NM_001190709.2		c.3051+15A>G	intron	N/A	NP_001177638.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.3168+15A>G	intron	N/A	ENSP00000359114.3
COL11A1	ENST00000512756.5	TSL:1	c.2820+15A>G	intron	N/A	ENSP00000426533.1
COL11A1	ENST00000635193.1	TSL:1	n.*418+15A>G	intron	N/A	ENSP00000489428.1

Frequencies

GnomAD3 genomes

AF:

0.0558

AC:

8485

AN:

152114

Hom.:

269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0405

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0438

Gnomad ASJ

AF:

0.0395

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0221

Gnomad FIN

AF:

0.0599

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0741

Gnomad OTH

AF:

0.0566

GnomAD2 exomes

AF:

0.0518

AC:

12898

AN:

249076

AF XY:

0.0516

show subpopulations

Gnomad AFR exome

AF:

0.0380

Gnomad AMR exome

AF:

0.0281

Gnomad ASJ exome

AF:

0.0422

Gnomad EAS exome

AF:

0.00868

Gnomad FIN exome

AF:

0.0596

Gnomad NFE exome

AF:

0.0747

Gnomad OTH exome

AF:

0.0563

GnomAD4 exome

AF:

0.0678

AC:

98559

AN:

1454742

Hom.:

3760

Cov.:

AF XY:

0.0665

AC XY:

48152

AN XY:

724020

show subpopulations

African (AFR)

AF:

0.0349

AC:

1164

AN:

33384

American (AMR)

AF:

0.0294

AC:

1311

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

1177

AN:

26034

East Asian (EAS)

AF:

0.00900

AC:

357

AN:

39670

South Asian (SAS)

AF:

0.0253

AC:

2171

AN:

85868

European-Finnish (FIN)

AF:

0.0596

AC:

3179

AN:

53318

Middle Eastern (MID)

AF:

0.0488

AC:

280

AN:

5742

European-Non Finnish (NFE)

AF:

0.0771

AC:

85319

AN:

1106020

Other (OTH)

AF:

0.0599

AC:

3601

AN:

60134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

3952

7904

11857

15809

19761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3066

6132

9198

12264

15330

<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:

0.0558

AC:

8493

AN:

152232

Hom.:

269

Cov.:

AF XY:

0.0547

AC XY:

4074

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0404

AC:

1679

AN:

41526

American (AMR)

AF:

0.0438

AC:

669

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0395

AC:

137

AN:

3470

East Asian (EAS)

AF:

0.0114

AC:

AN:

5178

South Asian (SAS)

AF:

0.0226

AC:

109

AN:

4830

European-Finnish (FIN)

AF:

0.0599

AC:

636

AN:

10612

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0741

AC:

5040

AN:

68018

Other (OTH)

AF:

0.0575

AC:

121

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

403

806

1208

1611

2014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0666

Hom.:

230

Bravo

AF:

0.0542

Asia WGS

AF:

0.0430

AC:

149

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Fibrochondrogenesis 1 (1)

Stickler syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over