chr1-102938828-T-C

Variant names:

• chr1-102938828-T-C
• rs2126643
• NM_001854.4:c.3438+207A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001854.4(COL11A1):​c.3438+207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,924 control chromosomes in the GnomAD database, including 30,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.63 (30554 hom., cov: 31)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.533
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-102938828-T-C is Benign according to our data. Variant chr1-102938828-T-C is described in ClinVar as Benign. ClinVar VariationId is 1282812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 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.3438+207A>G		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.3474+207A>G		intron	N/A	NP_542196.2
	COL11A1	NM_001190709.2		c.3321+207A>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.3438+207A>G		intron	N/A	ENSP00000359114.3
	COL11A1	ENST00000512756.5	TSL:1	c.3090+207A>G		intron	N/A	ENSP00000426533.1
	COL11A1	ENST00000635193.1	TSL:1	n.*688+207A>G		intron	N/A	ENSP00000489428.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95492 AN: 151806 Hom.: 30542 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.629 AC: 95543 AN: 151924 Hom.: 30554 Cov.: 31 AF XY: 0.629 AC XY: 46686 AN XY: 74246

African (AFR) AF: 0.518 AC: 21459 AN: 41438

American (AMR) AF: 0.679 AC: 10361 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2121 AN: 3468

East Asian (EAS) AF: 0.868 AC: 4488 AN: 5172

South Asian (SAS) AF: 0.747 AC: 3600 AN: 4822

European-Finnish (FIN) AF: 0.605 AC: 6369 AN: 10532

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.662 AC: 44963 AN: 67920

Other (OTH) AF: 0.631 AC: 1328 AN: 2106

Alfa AF: 0.651 Hom.: 49277

Bravo AF: 0.627

Asia WGS AF: 0.782 AC: 2700 AN: 3452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.78
PhyloP100		0.53
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: rs2126643; hg19: chr1-103404384; COSMIC: COSV62177053;