1-103098885-C-T

Variant names:

• chr1-103098885-C-T
• rs1415359
• NM_001854.4:c.106+9188G>A

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+9188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 151,356 control chromosomes in the GnomAD database, including 31,193 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 0.64 (31193 hom., cov: 31)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001854.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	NM_001854.4	MANE Select	c.106+9188G>A		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.106+9188G>A		intron	N/A	NP_542196.2
	COL11A1	NM_001190709.2		c.106+9188G>A		intron	N/A	NP_001177638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.106+9188G>A		intron	N/A	ENSP00000359114.3
	COL11A1	ENST00000512756.5	TSL:1	c.106+9188G>A		intron	N/A	ENSP00000426533.1
	COL11A1	ENST00000358392.6	TSL:5	c.106+9188G>A		intron	N/A	ENSP00000351163.2

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96627 AN: 151238 Hom.: 31174 Cov.: 31

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.679

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.639 AC: 96697 AN: 151356 Hom.: 31193 Cov.: 31 AF XY: 0.640 AC XY: 47313 AN XY: 73952

African (AFR) AF: 0.588 AC: 24318 AN: 41342

American (AMR) AF: 0.705 AC: 10676 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2200 AN: 3462

East Asian (EAS) AF: 0.916 AC: 4723 AN: 5158

South Asian (SAS) AF: 0.743 AC: 3581 AN: 4820

European-Finnish (FIN) AF: 0.572 AC: 6027 AN: 10532

Middle Eastern (MID) AF: 0.683 AC: 198 AN: 290

European-Non Finnish (NFE) AF: 0.636 AC: 43008 AN: 67600

Other (OTH) AF: 0.677 AC: 1419 AN: 2096

Alfa AF: 0.628 Hom.: 4964

Bravo AF: 0.648

Asia WGS AF: 0.811 AC: 2819 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.22
PhyloP100		0.17
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: rs1415359; hg19: chr1-103564441; COSMIC: COSV62177283; COSMIC: COSV62177283;