rs1415363

Variant names:

• chr1-103087379-A-G
• rs1415363
• NM_001854.4:c.107-4407T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-103087379-A-G
• chr1-103087379-A-T

Variant summary

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

The ENST00000370096.9(COL11A1):​c.107-4407T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,142 control chromosomes in the GnomAD database, including 47,891 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 0.79 (47891 hom., cov: 32)
• Consequence: COL11A1 ENST00000370096.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370096.9. 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.107-4407T>C		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.107-4407T>C		intron	N/A	NP_542196.2
	COL11A1	NM_001190709.2		c.107-4407T>C		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.107-4407T>C		intron	N/A	ENSP00000359114.3
	COL11A1	ENST00000512756.5	TSL:1	c.107-4407T>C		intron	N/A	ENSP00000426533.1
	COL11A1	ENST00000358392.6	TSL:5	c.107-4407T>C		intron	N/A	ENSP00000351163.2

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120250 AN: 152024 Hom.: 47851 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.812

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.791 AC: 120347 AN: 152142 Hom.: 47891 Cov.: 32 AF XY: 0.790 AC XY: 58742 AN XY: 74364

African (AFR) AF: 0.842 AC: 34957 AN: 41516

American (AMR) AF: 0.805 AC: 12313 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2578 AN: 3472

East Asian (EAS) AF: 0.985 AC: 5096 AN: 5172

South Asian (SAS) AF: 0.835 AC: 4022 AN: 4818

European-Finnish (FIN) AF: 0.693 AC: 7321 AN: 10566

Middle Eastern (MID) AF: 0.815 AC: 238 AN: 292

European-Non Finnish (NFE) AF: 0.757 AC: 51505 AN: 67998

Other (OTH) AF: 0.812 AC: 1711 AN: 2108

Alfa AF: 0.770 Hom.: 75254

Bravo AF: 0.802

Asia WGS AF: 0.900 AC: 3126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.0
DANN	Benign	0.80
PhyloP100		0.50
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: rs1415363; hg19: chr1-103552935;