1-102876928-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001854.4(COL11A1):c.*1091A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 152,548 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (0 hom.)
• Consequence: COL11A1 NM_001854.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.0630

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 1-102876928-T-A is Benign according to our data. Variant chr1-102876928-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 291479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00181 (276/152176) while in subpopulation NFE AF= 0.00281 (191/67954). AF 95% confidence interval is 0.00248. There are 1 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.*1091A>T		3_prime_UTR_variant	67/67	ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.*1091A>T		3_prime_UTR_variant	67/67	1	NM_001854.4	P1
COL11A1	ENST00000353414.8	c.*1091A>T		3_prime_UTR_variant	66/66	5
COL11A1	ENST00000358392.6	c.*1091A>T		3_prime_UTR_variant	67/67	5

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 276 AN: 152058 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00281

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.00269 AC: 1 AN: 372 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 226

Gnomad4 FIN exome AF: 0.00273

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00181 AC: 276 AN: 152176 Hom.: 1 Cov.: 32 AF XY: 0.00195 AC XY: 145 AN XY: 74406

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.00281

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00228 Hom.: 0

Bravo AF: 0.00148

Asia WGS AF: 0.000580 AC: 2 AN: 3462

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Fibrochondrogenesis 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Stickler syndrome type 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 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	-0.60
Cadd	Benign	3.0
Dann	Benign	0.66

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: rs41292523; hg19: chr1-103342484;