1-102913704-T-A

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.3979-14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,611,876 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0064 ( 62 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -6.74

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

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=-0.93).
BP6
Variant 1-102913704-T-A is Benign according to our data. Variant chr1-102913704-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 258463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00404 (615/152178) while in subpopulation SAS AF = 0.0127 (61/4818). AF 95% confidence interval is 0.0101. There are 3 homozygotes in GnomAd4. There are 282 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL11A1NM_001854.4 linkc.3979-14A>T intron_variant Intron 52 of 66 ENST00000370096.9 NP_001845.3 P12107-1Q59HB5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL11A1ENST00000370096.9 linkc.3979-14A>T intron_variant Intron 52 of 66 1 NM_001854.4 ENSP00000359114.3 P12107-1

Frequencies

GnomAD3 genomes
AF:
0.00405
AC:
616
AN:
152058
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00109
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00210
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0129
Gnomad FIN
AF:
0.00189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00653
Gnomad OTH
AF:
0.00143
GnomAD2 exomes
AF:
0.00521
AC:
1310
AN:
251270
AF XY:
0.00599
show subpopulations
Gnomad AFR exome
AF:
0.00111
Gnomad AMR exome
AF:
0.00104
Gnomad ASJ exome
AF:
0.00318
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00213
Gnomad NFE exome
AF:
0.00617
Gnomad OTH exome
AF:
0.00326
GnomAD4 exome
AF:
0.00640
AC:
9344
AN:
1459698
Hom.:
62
Cov.:
29
AF XY:
0.00662
AC XY:
4809
AN XY:
726338
show subpopulations
African (AFR)
AF:
0.000868
AC:
29
AN:
33402
American (AMR)
AF:
0.00110
AC:
49
AN:
44686
Ashkenazi Jewish (ASJ)
AF:
0.00276
AC:
72
AN:
26092
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39564
South Asian (SAS)
AF:
0.0151
AC:
1302
AN:
86206
European-Finnish (FIN)
AF:
0.00305
AC:
163
AN:
53406
Middle Eastern (MID)
AF:
0.00330
AC:
19
AN:
5760
European-Non Finnish (NFE)
AF:
0.00655
AC:
7268
AN:
1110286
Other (OTH)
AF:
0.00733
AC:
442
AN:
60296
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.459
Heterozygous variant carriers
0
408
815
1223
1630
2038
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
280
560
840
1120
1400
<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:
0.00404
AC:
615
AN:
152178
Hom.:
3
Cov.:
32
AF XY:
0.00379
AC XY:
282
AN XY:
74414
show subpopulations
African (AFR)
AF:
0.00108
AC:
45
AN:
41524
American (AMR)
AF:
0.00209
AC:
32
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00259
AC:
9
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5180
South Asian (SAS)
AF:
0.0127
AC:
61
AN:
4818
European-Finnish (FIN)
AF:
0.00189
AC:
20
AN:
10600
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00653
AC:
444
AN:
67984
Other (OTH)
AF:
0.00142
AC:
3
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
26
52
78
104
130
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00216
Hom.:
1
Bravo
AF:
0.00354
Asia WGS
AF:
0.00404
AC:
14
AN:
3476

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
-
Clinical Genetics, Academic Medical Center
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

-
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Oct 28, 2016
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. -

not provided Benign:3
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Apr 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

COL11A1: BS1, BS2 -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Fibrochondrogenesis 1 Benign:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Stickler syndrome type 2 Benign:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.0020
DANN
Benign
0.40
PhyloP100
-6.7
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs186245518; hg19: chr1-103379260; API