rs55682104

Variant names:

• chr1-102962288-T-A
• rs55682104
• NM_001854.4:c.3025-23A>T

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.3025-23A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,545,698 control chromosomes in the GnomAD database, including 8,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.080 (680 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8308 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.54
• 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Genomics England PanelApp
• Stickler syndrome type 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet
• fibrochondrogenesis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hearing loss, autosomal dominant 37

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• 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: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 5 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-102962288-T-A is Benign according to our data. Variant chr1-102962288-T-A is described in ClinVar as Benign. ClinVar VariationId is 258454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	NM_001854.4	MANE Select	c.3025-23A>T		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.3061-23A>T		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.2908-23A>T		intron	N/A	NP_001177638.1	P12107-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.3025-23A>T		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.2677-23A>T		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000635193.1	TSL:1	n.*275-23A>T		intron	N/A	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes AF: 0.0800 AC: 12164 AN: 152044 Hom.: 681 Cov.: 32

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0712

GnomAD2 exomes AF: 0.0927 AC: 23239 AN: 250790 AF XY: 0.0984

Gnomad AFR exome AF: 0.0181

Gnomad AMR exome AF: 0.0365

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.00337

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.0989

GnomAD4 exome AF: 0.104 AC: 145389 AN: 1393536 Hom.: 8308 Cov.: 23 AF XY: 0.106 AC XY: 73934 AN XY: 697688

African (AFR) AF: 0.0162 AC: 519 AN: 32030

American (AMR) AF: 0.0382 AC: 1704 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3515 AN: 25708

East Asian (EAS) AF: 0.00153 AC: 60 AN: 39344

South Asian (SAS) AF: 0.124 AC: 10493 AN: 84894

European-Finnish (FIN) AF: 0.141 AC: 7501 AN: 53384

Middle Eastern (MID) AF: 0.104 AC: 588 AN: 5648

European-Non Finnish (NFE) AF: 0.110 AC: 115208 AN: 1049860

Other (OTH) AF: 0.0999 AC: 5801 AN: 58080

GnomAD4 genome AF: 0.0799 AC: 12162 AN: 152162 Hom.: 680 Cov.: 32 AF XY: 0.0816 AC XY: 6070 AN XY: 74378

African (AFR) AF: 0.0188 AC: 779 AN: 41520

American (AMR) AF: 0.0523 AC: 799 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3472

East Asian (EAS) AF: 0.00406 AC: 21 AN: 5170

South Asian (SAS) AF: 0.110 AC: 531 AN: 4824

European-Finnish (FIN) AF: 0.150 AC: 1586 AN: 10586

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7529 AN: 67980

Other (OTH) AF: 0.0705 AC: 149 AN: 2114

Alfa AF: 0.105 Hom.: 198

Bravo AF: 0.0676

Asia WGS AF: 0.0370 AC: 133 AN: 3478

ClinVar

ClinVar submissions

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	-0.80
CADD	Benign	9.7
DANN	Benign	0.54
PhyloP100		1.5
La Branchor		0.74
BranchPoint Hunter		5.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs55682104;

hg19: chr1-103427844;