rs1012282

Variant names:

• chr1-102961825-A-G
• rs1012282
• NM_001854.4:c.3168+41T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080629.3(COL11A1):​c.3204+41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,571,308 control chromosomes in the GnomAD database, including 55,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6451 hom., cov: 32)
  • Exomes 𝑓: 0.26 (48932 hom.)
• Consequence: COL11A1 NM_080629.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.49
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-102961825-A-G is Benign according to our data. Variant chr1-102961825-A-G is described in ClinVar as Benign. ClinVar VariationId is 258456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080629.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	NM_001854.4	MANE Select	c.3168+41T>C		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.3204+41T>C		intron	N/A	NP_542196.2
	COL11A1	NM_001190709.2		c.3051+41T>C		intron	N/A	NP_001177638.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.3168+41T>C		intron	N/A	ENSP00000359114.3
	COL11A1	ENST00000512756.5	TSL:1	c.2820+41T>C		intron	N/A	ENSP00000426533.1
	COL11A1	ENST00000635193.1	TSL:1	n.*418+41T>C		intron	N/A	ENSP00000489428.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43023 AN: 152016 Hom.: 6440 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.248 AC: 60776 AN: 244704 AF XY: 0.243

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.0884

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.258 AC: 365859 AN: 1419174 Hom.: 48932 Cov.: 24 AF XY: 0.255 AC XY: 180607 AN XY: 708108

African (AFR) AF: 0.386 AC: 12652 AN: 32752

American (AMR) AF: 0.272 AC: 11972 AN: 44080

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 5927 AN: 25732

East Asian (EAS) AF: 0.0745 AC: 2945 AN: 39512

South Asian (SAS) AF: 0.168 AC: 14180 AN: 84574

European-Finnish (FIN) AF: 0.271 AC: 14398 AN: 53052

Middle Eastern (MID) AF: 0.292 AC: 1656 AN: 5672

European-Non Finnish (NFE) AF: 0.267 AC: 286961 AN: 1074876

Other (OTH) AF: 0.257 AC: 15168 AN: 58924

GnomAD4 genome AF: 0.283 AC: 43081 AN: 152134 Hom.: 6451 Cov.: 32 AF XY: 0.280 AC XY: 20829 AN XY: 74376

African (AFR) AF: 0.381 AC: 15803 AN: 41502

American (AMR) AF: 0.250 AC: 3821 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 769 AN: 3472

East Asian (EAS) AF: 0.0864 AC: 447 AN: 5172

South Asian (SAS) AF: 0.162 AC: 782 AN: 4832

European-Finnish (FIN) AF: 0.271 AC: 2868 AN: 10602

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17848 AN: 67978

Other (OTH) AF: 0.260 AC: 548 AN: 2108

Alfa AF: 0.276 Hom.: 10822

Bravo AF: 0.288

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Fibrochondrogenesis 1 (1)
-	-	1	Hearing loss, autosomal dominant 37 (1)
-	-	1	Marshall syndrome (1)
-	-	1	not specified (1)
-	-	1	Stickler syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs1012282; hg19: chr1-103427381;