rs17461252

Variant names:

• chr1-103017802-T-A
• rs17461252
• NM_001854.4:c.1413+18A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-103017802-T-A
• chr1-103017802-T-C

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+18A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 1,596,772 control chromosomes in the GnomAD database, including 3,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (219 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2830 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.50
• Publications: 7 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=-0.9).
• BP6: Variant 1-103017802-T-A is Benign according to our data. Variant chr1-103017802-T-A is described in ClinVar as Benign. ClinVar VariationId is 258439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0696 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+18A>T		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.1449+18A>T		intron	N/A	NP_542196.2
	COL11A1	NM_001190709.2		c.1296+18A>T		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+18A>T		intron	N/A	ENSP00000359114.3
	COL11A1	ENST00000512756.5	TSL:1	c.1065+18A>T		intron	N/A	ENSP00000426533.1
	COL11A1	ENST00000635193.1	TSL:1	n.729+18A>T		intron	N/A	ENSP00000489428.1

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6220 AN: 152082 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0577

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0547 AC: 13751 AN: 251190 AF XY: 0.0507

Gnomad AFR exome AF: 0.0119

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.00120

Gnomad FIN exome AF: 0.0534

Gnomad NFE exome AF: 0.0561

Gnomad OTH exome AF: 0.0467

GnomAD4 exome AF: 0.0562 AC: 81198 AN: 1444572 Hom.: 2830 Cov.: 29 AF XY: 0.0550 AC XY: 39600 AN XY: 719804

African (AFR) AF: 0.00880 AC: 292 AN: 33174

American (AMR) AF: 0.135 AC: 6046 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 278 AN: 26016

East Asian (EAS) AF: 0.00227 AC: 90 AN: 39618

South Asian (SAS) AF: 0.0239 AC: 2051 AN: 85956

European-Finnish (FIN) AF: 0.0570 AC: 3043 AN: 53400

Middle Eastern (MID) AF: 0.0125 AC: 71 AN: 5692

European-Non Finnish (NFE) AF: 0.0605 AC: 66318 AN: 1096238

Other (OTH) AF: 0.0503 AC: 3009 AN: 59784

GnomAD4 genome AF: 0.0409 AC: 6221 AN: 152200 Hom.: 219 Cov.: 32 AF XY: 0.0406 AC XY: 3019 AN XY: 74402

African (AFR) AF: 0.0108 AC: 450 AN: 41548

American (AMR) AF: 0.0731 AC: 1116 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5172

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4820

European-Finnish (FIN) AF: 0.0488 AC: 518 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0577 AC: 3924 AN: 68000

Other (OTH) AF: 0.0241 AC: 51 AN: 2112

Alfa AF: 0.0464 Hom.: 38

Bravo AF: 0.0423

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Oct 11, 2016

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.

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.90
CADD	Benign	0.52
DANN	Benign	0.46
PhyloP100		-2.5
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: rs17461252; hg19: chr1-103483358;