rs9659030

Variant names:

• chr1-102876836-T-C
• rs9659030
• NM_001854.4:c.*1183A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-102876836-T-C
• chr1-102876836-T-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.*1183A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,138 control chromosomes in the GnomAD database, including 3,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3063 hom., cov: 32)
  • Exomes 𝑓: 0.22 (5 hom.)
• Consequence: COL11A1 NM_001854.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.29
• Publications: 20 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), Genomics England PanelApp, Orphanet, G2P
• Stickler syndrome type 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P
• 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 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: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 1-102876836-T-C is Benign according to our data. Variant chr1-102876836-T-C is described in ClinVar as Benign. ClinVar VariationId is 291477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 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.*1183A>G		3_prime_UTR	Exon 67 of 67	NP_001845.3
	COL11A1	NM_080629.3		c.*1183A>G		3_prime_UTR	Exon 67 of 67	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.*1183A>G		3_prime_UTR	Exon 66 of 66	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.*1183A>G		3_prime_UTR	Exon 67 of 67	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000358392.6	TSL:5	c.*1183A>G		3_prime_UTR	Exon 67 of 67	ENSP00000351163.2	P12107-2
	COL11A1	ENST00000353414.8	TSL:5	c.*1183A>G		3_prime_UTR	Exon 66 of 66	ENSP00000302551.6	P12107-3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29742 AN: 151870 Hom.: 3066 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.220 AC: 33 AN: 150 Hom.: 5 Cov.: 0 AF XY: 0.222 AC XY: 20 AN XY: 90

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.219 AC: 32 AN: 146

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.196 AC: 29753 AN: 151988 Hom.: 3063 Cov.: 32 AF XY: 0.194 AC XY: 14444 AN XY: 74316

African (AFR) AF: 0.175 AC: 7269 AN: 41514

American (AMR) AF: 0.192 AC: 2919 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 421 AN: 3472

East Asian (EAS) AF: 0.251 AC: 1295 AN: 5168

South Asian (SAS) AF: 0.299 AC: 1441 AN: 4820

European-Finnish (FIN) AF: 0.137 AC: 1447 AN: 10590

Middle Eastern (MID) AF: 0.145 AC: 41 AN: 282

European-Non Finnish (NFE) AF: 0.213 AC: 14484 AN: 67884

Other (OTH) AF: 0.172 AC: 363 AN: 2112

Alfa AF: 0.208 Hom.: 7652

Bravo AF: 0.197

Asia WGS AF: 0.258 AC: 887 AN: 3444

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	Stickler syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.8
DANN	Benign	0.70
PhyloP100		1.3
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: rs9659030; hg19: chr1-103342392;