NM_001854.4:c.106+702T>C

Variant names:

• chr1-103107371-A-G
• rs4338381
• NM_001854.4:c.106+702T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001854.4(COL11A1):​c.106+702T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 150,644 control chromosomes in the GnomAD database, including 9,361 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (9361 hom., cov: 26)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• Marshall syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• Stickler syndrome type 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Orphanet, Genomics England PanelApp
• fibrochondrogenesis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal dominant 37

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• fibrochondrogenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive Stickler syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4	c.106+702T>C		intron_variant	Intron 1 of 66	ENST00000370096.9	NP_001845.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9	c.106+702T>C		intron_variant	Intron 1 of 66	1	NM_001854.4	ENSP00000359114.3

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52512 AN: 150530 Hom.: 9357 Cov.: 26

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.0910

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.349 AC: 52546 AN: 150644 Hom.: 9361 Cov.: 26 AF XY: 0.348 AC XY: 25535 AN XY: 73468

African (AFR) AF: 0.353 AC: 14470 AN: 40988

American (AMR) AF: 0.293 AC: 4435 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1299 AN: 3454

East Asian (EAS) AF: 0.0910 AC: 455 AN: 5000

South Asian (SAS) AF: 0.280 AC: 1322 AN: 4722

European-Finnish (FIN) AF: 0.434 AC: 4484 AN: 10338

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.369 AC: 24960 AN: 67694

Other (OTH) AF: 0.303 AC: 636 AN: 2098

Alfa AF: 0.341 Hom.: 5191

Bravo AF: 0.334

Asia WGS AF: 0.191 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		1.3
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs4338381; hg19: chr1-103572927;