chr1-103021688-T-C

Variant names:

• chr1-103021688-T-C
• rs34587338
• NM_001854.4:c.1308+19A>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.1308+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 1,562,682 control chromosomes in the GnomAD database, including 3,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (531 hom., cov: 30)
  • Exomes 𝑓: 0.062 (2919 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0400
• Publications: 5 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=-0.83).
• BP6: Variant 1-103021688-T-C is Benign according to our data. Variant chr1-103021688-T-C is described in ClinVar as Benign. ClinVar VariationId is 93965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 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.1308+19A>G		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.1344+19A>G		intron	N/A	NP_542196.2
	COL11A1	NM_001190709.2		c.1191+19A>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.1308+19A>G		intron	N/A	ENSP00000359114.3
	COL11A1	ENST00000512756.5	TSL:1	c.960+19A>G		intron	N/A	ENSP00000426533.1
	COL11A1	ENST00000635193.1	TSL:1	n.624+19A>G		intron	N/A	ENSP00000489428.1

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 11992 AN: 151992 Hom.: 528 Cov.: 30

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.0730

Gnomad EAS AF: 0.0721

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0789

GnomAD2 exomes AF: 0.0706 AC: 17752 AN: 251340 AF XY: 0.0704

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.0545

Gnomad ASJ exome AF: 0.0822

Gnomad EAS exome AF: 0.0797

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0615

Gnomad OTH exome AF: 0.0705

GnomAD4 exome AF: 0.0619 AC: 87313 AN: 1410572 Hom.: 2919 Cov.: 25 AF XY: 0.0621 AC XY: 43786 AN XY: 705182

African (AFR) AF: 0.118 AC: 3814 AN: 32274

American (AMR) AF: 0.0555 AC: 2480 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 2046 AN: 25824

East Asian (EAS) AF: 0.0638 AC: 2515 AN: 39440

South Asian (SAS) AF: 0.0671 AC: 5722 AN: 85306

European-Finnish (FIN) AF: 0.0994 AC: 5306 AN: 53364

Middle Eastern (MID) AF: 0.0936 AC: 531 AN: 5674

European-Non Finnish (NFE) AF: 0.0571 AC: 60839 AN: 1065274

Other (OTH) AF: 0.0691 AC: 4060 AN: 58752

GnomAD4 genome AF: 0.0790 AC: 12023 AN: 152110 Hom.: 531 Cov.: 30 AF XY: 0.0803 AC XY: 5975 AN XY: 74388

African (AFR) AF: 0.114 AC: 4712 AN: 41486

American (AMR) AF: 0.0661 AC: 1011 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0730 AC: 253 AN: 3468

East Asian (EAS) AF: 0.0723 AC: 374 AN: 5172

South Asian (SAS) AF: 0.0725 AC: 349 AN: 4816

European-Finnish (FIN) AF: 0.103 AC: 1094 AN: 10572

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0591 AC: 4017 AN: 67988

Other (OTH) AF: 0.0785 AC: 166 AN: 2114

Alfa AF: 0.0717 Hom.: 87

Bravo AF: 0.0793

Asia WGS AF: 0.0690 AC: 238 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 04, 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.

Sep 26, 2013

Eurofins Ntd Llc (ga)

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

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

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	-0.83
CADD	Benign	4.1
DANN	Benign	0.44
PhyloP100		0.040
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: rs34587338; hg19: chr1-103487244; COSMIC: COSV62191545;