rs71664954

Variant names:

• chr1-103004433-A-G
• rs71664954
• NM_001854.4:c.1944+11T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001854.4(COL11A1):​c.1944+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 1,602,428 control chromosomes in the GnomAD database, including 783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (62 hom., cov: 32)
  • Exomes 𝑓: 0.028 (721 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.414

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 1-103004433-A-G is Benign according to our data. Variant chr1-103004433-A-G is described in ClinVar as [Benign]. Clinvar id is 195479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-103004433-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4	c.1944+11T>C		intron_variant	Intron 20 of 66	ENST00000370096.9	NP_001845.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9	c.1944+11T>C		intron_variant	Intron 20 of 66	1	NM_001854.4	ENSP00000359114.3

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3660 AN: 152118 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.0664

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.0299 AC: 7464 AN: 249280 AF XY: 0.0321

Gnomad AFR exome AF: 0.0128

Gnomad AMR exome AF: 0.0157

Gnomad ASJ exome AF: 0.0435

Gnomad EAS exome AF: 0.0746

Gnomad FIN exome AF: 0.00315

Gnomad NFE exome AF: 0.0283

Gnomad OTH exome AF: 0.0283

GnomAD4 exome AF: 0.0281 AC: 40759 AN: 1450192 Hom.: 721 Cov.: 29 AF XY: 0.0290 AC XY: 20909 AN XY: 721976

Gnomad4 AFR exome AF: 0.0142 AC: 471 AN: 33176

Gnomad4 AMR exome AF: 0.0165 AC: 737 AN: 44640

Gnomad4 ASJ exome AF: 0.0429 AC: 1114 AN: 25984

Gnomad4 EAS exome AF: 0.0592 AC: 2340 AN: 39540

Gnomad4 SAS exome AF: 0.0490 AC: 4196 AN: 85644

Gnomad4 FIN exome AF: 0.00420 AC: 224 AN: 53284

Gnomad4 NFE exome AF: 0.0269 AC: 29698 AN: 1103248

Gnomad4 Remaining exome AF: 0.0296 AC: 1775 AN: 59870

GnomAD4 genome AF: 0.0241 AC: 3672 AN: 152236 Hom.: 62 Cov.: 32 AF XY: 0.0240 AC XY: 1785 AN XY: 74432

Gnomad4 AFR AF: 0.0145 AC: 0.0144844 AN: 0.0144844

Gnomad4 AMR AF: 0.0272 AC: 0.027243 AN: 0.027243

Gnomad4 ASJ AF: 0.0424 AC: 0.0423875 AN: 0.0423875

Gnomad4 EAS AF: 0.0665 AC: 0.0665253 AN: 0.0665253

Gnomad4 SAS AF: 0.0536 AC: 0.0536454 AN: 0.0536454

Gnomad4 FIN AF: 0.00273 AC: 0.00273224 AN: 0.00273224

Gnomad4 NFE AF: 0.0262 AC: 0.0262229 AN: 0.0262229

Gnomad4 OTH AF: 0.0289 AC: 0.02891 AN: 0.02891

Alfa AF: 0.0263 Hom.: 17

Bravo AF: 0.0251

Asia WGS AF: 0.0440 AC: 151 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Oct 05, 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. -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 15, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Fibrochondrogenesis 1 Benign:1

Jan 13, 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 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.85
Mutation Taster		=99/1	polymorphism (auto)

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

LitVar

Other links and lift over

dbSNP: rs71664954; hg19: chr1-103469989;