rs4908273

Variant names:

• chr1-102915573-C-T
• rs4908273
• NM_001854.4:c.3816+58G>A

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.3816+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,415,680 control chromosomes in the GnomAD database, including 10,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1098 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9666 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.374
• Publications: 8 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=-0.85).
• BP6: Variant 1-102915573-C-T is Benign according to our data. Variant chr1-102915573-C-T is described in ClinVar as Benign. ClinVar VariationId is 1221542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4	c.3816+58G>A		intron_variant	Intron 50 of 66	ENST00000370096.9	NP_001845.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9	c.3816+58G>A		intron_variant	Intron 50 of 66	1	NM_001854.4	ENSP00000359114.3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17465 AN: 151976 Hom.: 1096 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.117 AC: 147837 AN: 1263586 Hom.: 9666 AF XY: 0.118 AC XY: 75623 AN XY: 639404

African (AFR) AF: 0.139 AC: 4099 AN: 29564

American (AMR) AF: 0.0949 AC: 4219 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.0705 AC: 1754 AN: 24896

East Asian (EAS) AF: 0.254 AC: 9820 AN: 38684

South Asian (SAS) AF: 0.178 AC: 14676 AN: 82316

European-Finnish (FIN) AF: 0.0578 AC: 3082 AN: 53292

Middle Eastern (MID) AF: 0.0885 AC: 478 AN: 5404

European-Non Finnish (NFE) AF: 0.111 AC: 103672 AN: 931178

Other (OTH) AF: 0.112 AC: 6037 AN: 53806

GnomAD4 genome AF: 0.115 AC: 17470 AN: 152094 Hom.: 1098 Cov.: 32 AF XY: 0.113 AC XY: 8386 AN XY: 74364

African (AFR) AF: 0.135 AC: 5612 AN: 41474

American (AMR) AF: 0.0884 AC: 1351 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1103 AN: 5152

South Asian (SAS) AF: 0.198 AC: 954 AN: 4830

European-Finnish (FIN) AF: 0.0491 AC: 521 AN: 10602

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7411 AN: 67972

Other (OTH) AF: 0.105 AC: 222 AN: 2110

Alfa AF: 0.112 Hom.: 568

Bravo AF: 0.116

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		-0.37
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: rs4908273; hg19: chr1-103381129; COSMIC: COSV62173323;