1-103005900-CCATCATCATCATCATCAT-CCATCATCATCAT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001854.4(COL11A1):c.1792-15_1792-10delATGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00756 in 1,336,324 control chromosomes in the GnomAD database, including 93 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 49 hom., cov: 0)

Exomes 𝑓: 0.0068 ( 44 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.41

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: 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 -16 ACMG points.

BP6

Variant 1-103005900-CCATCAT-C is Benign according to our data. Variant chr1-103005900-CCATCAT-C is described in ClinVar as Benign. ClinVar VariationId is 291531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0138 (2077/150322) while in subpopulation AFR AF = 0.0431 (1765/40982). AF 95% confidence interval is 0.0414. There are 49 homozygotes in GnomAd4. There are 987 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 49 AR,AD gene

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	UniProt
COL11A1	NM_001854.4	MANE Select	c.1792-15_1792-10delATGATG	intron	N/A	NP_001845.3
COL11A1	NM_080629.3		c.1828-15_1828-10delATGATG	intron	N/A	NP_542196.2	P12107-2
COL11A1	NM_001190709.2		c.1675-15_1675-10delATGATG	intron	N/A	NP_001177638.1	P12107-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.1792-15_1792-10delATGATG	intron	N/A	ENSP00000359114.3	P12107-1
COL11A1	ENST00000512756.5	TSL:1	c.1444-15_1444-10delATGATG	intron	N/A	ENSP00000426533.1	P12107-4
COL11A1	ENST00000635193.1	TSL:1	n.1108-15_1108-10delATGATG	intron	N/A	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2073

AN:

150208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.00460

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.000395

Gnomad SAS

AF:

0.00232

Gnomad FIN

AF:

0.00284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00274

Gnomad OTH

AF:

0.00778

GnomAD2 exomes

AF:

0.00707

AC:

1380

AN:

195300

AF XY:

0.00601

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.00455

Gnomad ASJ exome

AF:

0.000611

Gnomad EAS exome

AF:

0.00146

Gnomad FIN exome

AF:

0.00419

Gnomad NFE exome

AF:

0.00413

Gnomad OTH exome

AF:

0.00678

GnomAD4 exome

AF:

0.00677

AC:

8031

AN:

1186002

Hom.:

AF XY:

0.00627

AC XY:

3698

AN XY:

589506

show subpopulations

African (AFR)

AF:

0.0464

AC:

1418

AN:

30566

American (AMR)

AF:

0.00470

AC:

164

AN:

34874

Ashkenazi Jewish (ASJ)

AF:

0.00106

AC:

AN:

21734

East Asian (EAS)

AF:

0.00184

AC:

AN:

28844

South Asian (SAS)

AF:

0.00455

AC:

304

AN:

66826

European-Finnish (FIN)

AF:

0.00458

AC:

208

AN:

45406

Middle Eastern (MID)

AF:

0.0120

AC:

AN:

5076

European-Non Finnish (NFE)

AF:

0.00599

AC:

5412

AN:

903752

Other (OTH)

AF:

0.00793

AC:

388

AN:

48924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

383

767

1150

1534

1917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.0138

AC:

2077

AN:

150322

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

987

AN XY:

73256

show subpopulations

African (AFR)

AF:

0.0431

AC:

1765

AN:

40982

American (AMR)

AF:

0.00452

AC:

AN:

15030

Ashkenazi Jewish (ASJ)

AF:

0.000290

AC:

AN:

3450

East Asian (EAS)

AF:

0.000396

AC:

AN:

5056

South Asian (SAS)

AF:

0.00211

AC:

AN:

4732

European-Finnish (FIN)

AF:

0.00284

AC:

AN:

10228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00274

AC:

185

AN:

67568

Other (OTH)

AF:

0.00770

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

101

201

302

402

503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0629

Hom.:

3593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Fibrochondrogenesis 1 (1)

Marshall syndrome (1)

Stickler Syndrome, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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