rs1031820

Variant names:

• chr1-102877914-G-A
• rs1031820
• ENST00000635193.1:n.*2776C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-102877914-G-A
• chr1-102877914-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000635193.1(COL11A1):​n.*2776C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,157,586 control chromosomes in the GnomAD database, including 4,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (995 hom., cov: 31)
  • Exomes 𝑓: 0.080 (3704 hom.)
• Consequence: COL11A1 ENST00000635193.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.38
• Publications: 13 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=-0.71).
• BP6: Variant 1-102877914-G-A is Benign according to our data. Variant chr1-102877914-G-A is described in ClinVar as Benign. ClinVar VariationId is 291490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635193.1. 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.*105C>T		3_prime_UTR	Exon 67 of 67	NP_001845.3
	COL11A1	NR_134980.2		n.5886C>T		non_coding_transcript_exon	Exon 68 of 68
	COL11A1	NM_080629.3		c.*105C>T		3_prime_UTR	Exon 67 of 67	NP_542196.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	ENST00000635193.1	TSL:1	n.*2776C>T		non_coding_transcript_exon	Exon 64 of 64	ENSP00000489428.1
	COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.*105C>T		3_prime_UTR	Exon 67 of 67	ENSP00000359114.3
	COL11A1	ENST00000635193.1	TSL:1	n.*2776C>T		3_prime_UTR	Exon 64 of 64	ENSP00000489428.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16047 AN: 152024 Hom.: 998 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0988

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0912

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.0802 AC: 80603 AN: 1005444 Hom.: 3704 Cov.: 13 AF XY: 0.0794 AC XY: 41226 AN XY: 519100

African (AFR) AF: 0.160 AC: 3920 AN: 24534

American (AMR) AF: 0.0684 AC: 2950 AN: 43156

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 4387 AN: 22890

East Asian (EAS) AF: 0.0582 AC: 2158 AN: 37058

South Asian (SAS) AF: 0.0435 AC: 3307 AN: 75988

European-Finnish (FIN) AF: 0.0790 AC: 4082 AN: 51642

Middle Eastern (MID) AF: 0.158 AC: 716 AN: 4530

European-Non Finnish (NFE) AF: 0.0781 AC: 54747 AN: 700670

Other (OTH) AF: 0.0964 AC: 4336 AN: 44976

GnomAD4 genome AF: 0.105 AC: 16051 AN: 152142 Hom.: 995 Cov.: 31 AF XY: 0.103 AC XY: 7690 AN XY: 74376

African (AFR) AF: 0.157 AC: 6516 AN: 41502

American (AMR) AF: 0.0987 AC: 1509 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3470

East Asian (EAS) AF: 0.0674 AC: 349 AN: 5176

South Asian (SAS) AF: 0.0417 AC: 201 AN: 4824

European-Finnish (FIN) AF: 0.0912 AC: 965 AN: 10580

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0801 AC: 5443 AN: 67988

Other (OTH) AF: 0.132 AC: 278 AN: 2108

Alfa AF: 0.0686 Hom.: 118

Bravo AF: 0.110

Asia WGS AF: 0.0570 AC: 202 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Fibrochondrogenesis 1 (1)
-	-	1	Stickler syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.8
DANN	Benign	0.84
PhyloP100		2.4
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: rs1031820; hg19: chr1-103343470; COSMIC: COSV62183698; COSMIC: COSV62183698;