1-102876836-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001854.4(COL11A1):c.*1183A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,138 control chromosomes in the GnomAD database, including 3,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3063 hom., cov: 32)
  • Exomes 𝑓: 0.22 (5 hom.)
• Consequence: COL11A1 NM_001854.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.29

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 1-102876836-T-C is Benign according to our data. Variant chr1-102876836-T-C is described in ClinVar as [Benign]. Clinvar id is 291477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.*1183A>G		3_prime_UTR_variant	67/67	ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.*1183A>G		3_prime_UTR_variant	67/67	1	NM_001854.4	P1
COL11A1	ENST00000353414.8	c.*1183A>G		3_prime_UTR_variant	66/66	5
COL11A1	ENST00000358392.6	c.*1183A>G		3_prime_UTR_variant	67/67	5

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29742 AN: 151870 Hom.: 3066 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.220 AC: 33 AN: 150 Hom.: 5 Cov.: 0 AF XY: 0.222 AC XY: 20 AN XY: 90

Gnomad4 FIN exome AF: 0.219

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.196 AC: 29753 AN: 151988 Hom.: 3063 Cov.: 32 AF XY: 0.194 AC XY: 14444 AN XY: 74316

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.172

Alfa AF: 0.209 Hom.: 4838

Bravo AF: 0.197

Asia WGS AF: 0.258 AC: 887 AN: 3444

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fibrochondrogenesis 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Stickler syndrome type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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	-0.55
Cadd	Benign	5.8
Dann	Benign	0.70

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: rs9659030; hg19: chr1-103342392;