chr1-102963855-G-T

Variant names:

• chr1-102963855-G-T
• rs2615987
• NM_001854.4:c.2917-1095C>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.2917-1095C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,722 control chromosomes in the GnomAD database, including 6,504 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 0.28 (6504 hom., cov: 32)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 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.2917-1095C>A		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.2953-1095C>A		intron	N/A	NP_542196.2
	COL11A1	NM_001190709.2		c.2800-1095C>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.2917-1095C>A		intron	N/A	ENSP00000359114.3
	COL11A1	ENST00000512756.5	TSL:1	c.2569-1095C>A		intron	N/A	ENSP00000426533.1
	COL11A1	ENST00000635193.1	TSL:1	n.*167-1095C>A		intron	N/A	ENSP00000489428.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43163 AN: 151602 Hom.: 6490 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.285 AC: 43224 AN: 151722 Hom.: 6504 Cov.: 32 AF XY: 0.282 AC XY: 20909 AN XY: 74136

African (AFR) AF: 0.386 AC: 15938 AN: 41338

American (AMR) AF: 0.252 AC: 3842 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3468

East Asian (EAS) AF: 0.0870 AC: 449 AN: 5158

South Asian (SAS) AF: 0.161 AC: 777 AN: 4814

European-Finnish (FIN) AF: 0.273 AC: 2863 AN: 10490

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.263 AC: 17836 AN: 67886

Other (OTH) AF: 0.262 AC: 552 AN: 2104

Alfa AF: 0.217 Hom.: 721

Bravo AF: 0.289

Asia WGS AF: 0.166 AC: 574 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.66
PhyloP100		0.13
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: rs2615987; hg19: chr1-103429411;