rs55682104

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001854.4(COL11A1):c.3025-23A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,545,698 control chromosomes in the GnomAD database, including 8,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.080 ( 680 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8308 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.54

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 5 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-102962288-T-A is Benign according to our data. Variant chr1-102962288-T-A is described in ClinVar as [Benign]. Clinvar id is 258454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.3025-23A>T		intron_variant	Intron 39 of 66	ENST00000370096.9	NP_001845.3	P12107-1Q59HB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9 link	c.3025-23A>T		intron_variant	Intron 39 of 66	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.0800

AC:

12164

AN:

152044

Hom.:

681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.0523

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.00405

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.0712

GnomAD3 exomes

AF:

0.0927

AC:

23239

AN:

250790

Hom.:

1426

AF XY:

0.0984

AC XY:

13341

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.0365

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.00337

Gnomad SAS exome

AF:

0.120

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.114

Gnomad OTH exome

AF:

0.0989

GnomAD4 exome

AF:

0.104

AC:

145389

AN:

1393536

Hom.:

8308

Cov.:

AF XY:

0.106

AC XY:

73934

AN XY:

697688

show subpopulations

Gnomad4 AFR exome

AF:

0.0162

Gnomad4 AMR exome

AF:

0.0382

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.00153

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.0999

GnomAD4 genome

AF:

0.0799

AC:

12162

AN:

152162

Hom.:

680

Cov.:

AF XY:

0.0816

AC XY:

6070

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0188

Gnomad4 AMR

AF:

0.0523

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.00406

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.0705

Alfa

AF:

0.105

Hom.:

198

Bravo

AF:

0.0676

Asia WGS

AF:

0.0370

AC:

133

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hearing loss, autosomal dominant 37

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Marshall syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibrochondrogenesis 1

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Stickler syndrome type 2

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.7

DANN

Benign

0.54

La Branchor

0.74

BranchPoint Hunter

5.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over