rs115516103

chr1-102921104-G-Achr1-102921104-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001854.4(COL11A1):c.3708+414C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 152,148 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.033 (107 hom., cov: 33)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.839

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=-0.88).
• BP6: Variant 1-102921104-G-A is Benign according to our data. Variant chr1-102921104-G-A is described in ClinVar as [Benign]. Clinvar id is 585676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0326 (4960/152148) while in subpopulation NFE AF= 0.034 (2314/67976). AF 95% confidence interval is 0.0329. There are 107 homozygotes in gnomad4. There are 2464 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 106 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.3708+414C>T		intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.3708+414C>T		intron_variant		1	NM_001854.4	P1

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4954 AN: 152030 Hom.: 106 Cov.: 33

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0340

Gnomad OTH AF: 0.0368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0326 AC: 4960 AN: 152148 Hom.: 107 Cov.: 33 AF XY: 0.0331 AC XY: 2464 AN XY: 74376

Gnomad4 AFR AF: 0.0290

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.00579

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0598

Gnomad4 NFE AF: 0.0340

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.00785 Hom.: 2

Bravo AF: 0.0326

Asia WGS AF: 0.0220 AC: 76 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.73
Dann	Benign	0.46

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: rs115516103; hg19: chr1-103386660;