rs3767272

Variant names:

• chr1-103017773-T-C
• rs3767272
• NM_001854.4:c.1413+47A>G

Variant summary

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

The NM_001854.4(COL11A1):​c.1413+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,453,522 control chromosomes in the GnomAD database, including 734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (61 hom., cov: 32)
  • Exomes 𝑓: 0.028 (673 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0650
• Publications: 3 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=-0.89).
• BP6: Variant 1-103017773-T-C is Benign according to our data. Variant chr1-103017773-T-C is described in ClinVar as Benign. ClinVar VariationId is 674969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0611 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.1413+47A>G		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.1449+47A>G		intron	N/A	NP_542196.2
	COL11A1	NM_001190709.2		c.1296+47A>G		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.1413+47A>G		intron	N/A	ENSP00000359114.3
	COL11A1	ENST00000512756.5	TSL:1	c.1065+47A>G		intron	N/A	ENSP00000426533.1
	COL11A1	ENST00000635193.1	TSL:1	n.729+47A>G		intron	N/A	ENSP00000489428.1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3671 AN: 152100 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0291

GnomAD2 exomes AF: 0.0299 AC: 7509 AN: 250830 AF XY: 0.0321

Gnomad AFR exome AF: 0.0128

Gnomad AMR exome AF: 0.0159

Gnomad ASJ exome AF: 0.0435

Gnomad EAS exome AF: 0.0750

Gnomad FIN exome AF: 0.00315

Gnomad NFE exome AF: 0.0284

Gnomad OTH exome AF: 0.0285

GnomAD4 exome AF: 0.0284 AC: 36981 AN: 1301304 Hom.: 673 Cov.: 19 AF XY: 0.0293 AC XY: 19242 AN XY: 656534

African (AFR) AF: 0.0140 AC: 425 AN: 30378

American (AMR) AF: 0.0166 AC: 737 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 1082 AN: 25206

East Asian (EAS) AF: 0.0606 AC: 2359 AN: 38948

South Asian (SAS) AF: 0.0484 AC: 4022 AN: 83078

European-Finnish (FIN) AF: 0.00422 AC: 225 AN: 53294

Middle Eastern (MID) AF: 0.0419 AC: 219 AN: 5230

European-Non Finnish (NFE) AF: 0.0272 AC: 26281 AN: 965716

Other (OTH) AF: 0.0297 AC: 1631 AN: 54958

GnomAD4 genome AF: 0.0242 AC: 3683 AN: 152218 Hom.: 61 Cov.: 32 AF XY: 0.0241 AC XY: 1790 AN XY: 74406

African (AFR) AF: 0.0145 AC: 602 AN: 41550

American (AMR) AF: 0.0274 AC: 418 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3470

East Asian (EAS) AF: 0.0669 AC: 347 AN: 5186

South Asian (SAS) AF: 0.0536 AC: 259 AN: 4828

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10606

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0263 AC: 1790 AN: 67996

Other (OTH) AF: 0.0293 AC: 62 AN: 2116

Alfa AF: 0.0255 Hom.: 18

Bravo AF: 0.0252

Asia WGS AF: 0.0440 AC: 151 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.32
PhyloP100		0.065
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: rs3767272; hg19: chr1-103483329; COSMIC: COSV62189404;