Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001854.4(COL11A1):c.3924+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,585,818 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 57 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 41 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.282

Publications

1 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=-0.8).

BP6

Variant 1-102914685-G-A is Benign according to our data. Variant chr1-102914685-G-A is described in ClinVar as Benign. ClinVar VariationId is 258460.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 = 0.0136 (2065/152102) while in subpopulation AFR AF = 0.0474 (1967/41516). AF 95% confidence interval is 0.0456. There are 57 homozygotes in GnomAd4. There are 996 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 57 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
COL11A1	NM_001854.4	MANE Select	c.3924+19C>T	intron	N/A	NP_001845.3
COL11A1	NM_080629.3		c.3960+19C>T	intron	N/A	NP_542196.2
COL11A1	NM_001190709.2		c.3807+19C>T	intron	N/A	NP_001177638.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.3924+19C>T	intron	N/A	ENSP00000359114.3
COL11A1	ENST00000512756.5	TSL:1	c.3576+19C>T	intron	N/A	ENSP00000426533.1
COL11A1	ENST00000635193.1	TSL:1	n.*1174+19C>T	intron	N/A	ENSP00000489428.1

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2060

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0474

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00357

AC:

880

AN:

246720

AF XY:

0.00244

show subpopulations

Gnomad AFR exome

AF:

0.0496

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000540

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.00141

AC:

2027

AN:

1433716

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

847

AN XY:

714680

show subpopulations

African (AFR)

AF:

0.0504

AC:

1662

AN:

32954

American (AMR)

AF:

0.00236

AC:

105

AN:

44398

Ashkenazi Jewish (ASJ)

AF:

0.0000386

AC:

AN:

25894

East Asian (EAS)

AF:

0.00

AC:

AN:

39518

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53270

Middle Eastern (MID)

AF:

0.000953

AC:

AN:

5244

European-Non Finnish (NFE)

AF:

0.0000570

AC:

AN:

1087794

Other (OTH)

AF:

0.00322

AC:

191

AN:

59374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

197

295

394

492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.0136

AC:

2065

AN:

152102

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

996

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0474

AC:

1967

AN:

41516

American (AMR)

AF:

0.00471

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.000208

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67982

Other (OTH)

AF:

0.00994

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

186

280

373

466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00657

Hom.:

Bravo

AF:

0.0154

Asia WGS

AF:

0.00260

AC:

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 (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.2

(source)

DANN

Benign

0.48

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs77901108

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