dbSNP rs2229783: COL11A1:p.Ile1590Ile (chr1-102886895-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001854.4(COL11A1):c.4770T>C(p.Ile1590Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,613,456 control chromosomes in the GnomAD database, including 289,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 21765 hom., cov: 31)

Exomes 𝑓: 0.60 ( 267716 hom. )

Consequence

COL11A1
NM_001854.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.790

Publications

41 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P
Stickler syndrome type 2
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P
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 nonsyndromic hearing loss
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-102886895-A-G is Benign according to our data. Variant chr1-102886895-A-G is described in ClinVar as Benign. ClinVar VariationId is 258470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 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	HGVSp	Effect	Exon Rank	Protein	UniProt
COL11A1	NM_001854.4	MANE Select	c.4770T>C	p.Ile1590Ile	synonymous	Exon 63 of 67	NP_001845.3
COL11A1	NM_080629.3		c.4806T>C	p.Ile1602Ile	synonymous	Exon 63 of 67	NP_542196.2	P12107-2
COL11A1	NM_001190709.2		c.4653T>C	p.Ile1551Ile	synonymous	Exon 62 of 66	NP_001177638.1	P12107-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.4770T>C	p.Ile1590Ile	synonymous	Exon 63 of 67	ENSP00000359114.3	P12107-1
COL11A1	ENST00000512756.5	TSL:1	c.4422T>C	p.Ile1474Ile	synonymous	Exon 61 of 65	ENSP00000426533.1	P12107-4
COL11A1	ENST00000635193.1	TSL:1	n.*2020T>C		non_coding_transcript_exon	Exon 60 of 64	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74268

AN:

151790

Hom.:

21753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.637

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.665

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.639

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.617

Gnomad OTH

AF:

0.521

GnomAD2 exomes

AF:

0.593

AC:

149024

AN:

251204

AF XY:

0.596

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.734

Gnomad ASJ exome

AF:

0.556

Gnomad EAS exome

AF:

0.638

Gnomad FIN exome

AF:

0.648

Gnomad NFE exome

AF:

0.609

Gnomad OTH exome

AF:

0.611

GnomAD4 exome

AF:

0.600

AC:

876350

AN:

1461548

Hom.:

267716

Cov.:

AF XY:

0.600

AC XY:

436366

AN XY:

727072

show subpopulations

African (AFR)

AF:

0.117

AC:

3912

AN:

33464

American (AMR)

AF:

0.724

AC:

32351

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

14527

AN:

26126

East Asian (EAS)

AF:

0.630

AC:

25017

AN:

39682

South Asian (SAS)

AF:

0.573

AC:

49459

AN:

86256

European-Finnish (FIN)

AF:

0.649

AC:

34643

AN:

53414

Middle Eastern (MID)

AF:

0.562

AC:

3237

AN:

5764

European-Non Finnish (NFE)

AF:

0.610

AC:

677943

AN:

1111760

Other (OTH)

AF:

0.584

AC:

35261

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

20244

40488

60733

80977

101221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18152

36304

54456

72608

90760

<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:

0.489

AC:

74287

AN:

151908

Hom.:

21765

Cov.:

AF XY:

0.496

AC XY:

36817

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.137

AC:

5694

AN:

41470

American (AMR)

AF:

0.657

AC:

10010

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1957

AN:

3468

East Asian (EAS)

AF:

0.665

AC:

3408

AN:

5128

South Asian (SAS)

AF:

0.569

AC:

2741

AN:

4816

European-Finnish (FIN)

AF:

0.639

AC:

6726

AN:

10526

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.617

AC:

41900

AN:

67958

Other (OTH)

AF:

0.525

AC:

1107

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1589

3178

4766

6355

7944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.574

Hom.:

51869

Bravo

AF:

0.477

Asia WGS

AF:

0.591

AC:

2050

AN:

3476

EpiCase

AF:

0.605

EpiControl

AF:

0.604

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Fibrochondrogenesis 1 (2)

not provided (2)

Stickler syndrome type 2 (2)

Hearing loss, autosomal dominant 37 (1)

Marshall syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.24

(source)

DANN

Benign

0.68

PhyloP100

-0.79

Mutation Taster

=93/7

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

Computational scores

Splicing

Publications

Other links and lift over