1-103005900-CCATCATCATCATCATCAT-CCATCATCAT

Variant names:

• chr1-103005900-CCATCATCAT-C
• rs71752747
• NM_001854.4:c.1792-18_1792-10delATGATGATG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001854.4(COL11A1):​c.1792-18_1792-10delATGATGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000512 in 1,367,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000051 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.41
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 1-103005900-CCATCATCAT-C is Benign according to our data. Variant chr1-103005900-CCATCATCAT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1569144.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1792-18_1792-10delATGATGATG		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.1828-18_1828-10delATGATGATG		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.1675-18_1675-10delATGATGATG		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.1792-18_1792-10delATGATGATG		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.1444-18_1444-10delATGATGATG		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000635193.1	TSL:1	n.1108-18_1108-10delATGATGATG		intron	N/A	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150394 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000307 AC: 6 AN: 195300 AF XY: 0.0000380

Gnomad AFR exome AF: 0.0000710

Gnomad AMR exome AF: 0.000200

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000512 AC: 7 AN: 1367768 Hom.: 0 AF XY: 0.00000587 AC XY: 4 AN XY: 681382

African (AFR) AF: 0.00 AC: 0 AN: 32454

American (AMR) AF: 0.000118 AC: 5 AN: 42212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24942

East Asian (EAS) AF: 0.00 AC: 0 AN: 36548

South Asian (SAS) AF: 0.00 AC: 0 AN: 81056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5538

European-Non Finnish (NFE) AF: 9.64e-7 AC: 1 AN: 1037264

Other (OTH) AF: 0.0000177 AC: 1 AN: 56640

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150394 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73240

African (AFR) AF: 0.00 AC: 0 AN: 40880

American (AMR) AF: 0.00 AC: 0 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.00 AC: 0 AN: 4740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67646

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 3593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71752747; hg19: chr1-103471456;