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rs187171126

chr1-102898931-T-Achr1-102898931-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001854.4(COL11A1):c.4140+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,387,794 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 19 hom., cov: 32)
Exomes 𝑓: 0.00078 ( 13 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -2.17
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-102898931-T-A is Benign according to our data. Variant chr1-102898931-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 166921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-102898931-T-A is described in Lovd as [Benign].
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00826 (1207/146066) while in subpopulation AFR AF= 0.0283 (1142/40364). AF 95% confidence interval is 0.0269. There are 19 homozygotes in gnomad4. There are 558 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 19 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL11A1NM_001854.4 linkuse as main transcriptc.4140+10A>T intron_variant ENST00000370096.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL11A1ENST00000370096.9 linkuse as main transcriptc.4140+10A>T intron_variant 1 NM_001854.4 P1P12107-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00825
AC:
1205
AN:
146050
Hom.:
19
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0283
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00301
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000216
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000758
Gnomad OTH
AF:
0.00761
GnomAD3 exomes
AF:
0.00190
AC:
385
AN:
203156
Hom.:
7
AF XY:
0.00131
AC XY:
147
AN XY:
111908
show subpopulations
Gnomad AFR exome
AF:
0.0280
Gnomad AMR exome
AF:
0.000923
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000121
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000120
Gnomad OTH exome
AF:
0.00105
GnomAD4 exome
AF:
0.000777
AC:
965
AN:
1241728
Hom.:
13
Cov.:
19
AF XY:
0.000702
AC XY:
436
AN XY:
621230
show subpopulations
Gnomad4 AFR exome
AF:
0.0270
Gnomad4 AMR exome
AF:
0.00143
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000123
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000640
Gnomad4 OTH exome
AF:
0.00180
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00826
AC:
1207
AN:
146066
Hom.:
19
Cov.:
32
AF XY:
0.00784
AC XY:
558
AN XY:
71200
show subpopulations
Gnomad4 AFR
AF:
0.0283
Gnomad4 AMR
AF:
0.00301
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000217
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000759
Gnomad4 OTH
AF:
0.00757
Alfa
AF:
0.00428
Hom.:
2
Bravo
AF:
0.00929
Asia WGS
AF:
0.000581
AC:
2
AN:
3458

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
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Apr 28, 2014- -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxApr 13, 2018- -
Fibrochondrogenesis 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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. -
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingCenter for Human Genetics, Inc, Center for Human Genetics, IncNov 01, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
Cadd
Benign
0.037
Dann
Benign
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs187171126; hg19: chr1-103364487; API