1-103005900-CCATCATCATCATCATCAT-CCATCATCATCATCATCATCAT

Variant names:

• chr1-103005900-C-CCAT
• rs71752747
• NM_001854.4:c.1792-12_1792-10dupATG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001854.4(COL11A1):​c.1792-12_1792-10dupATG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.022 (100 hom., cov: 0)
  • Exomes 𝑓: 0.0057 (53 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4 B:7
• Conservation: PhyloP100: -0.166
• 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: Benign. The variant received -9 ACMG points.

• BP6: Variant 1-103005900-C-CCAT is Benign according to our data. Variant chr1-103005900-C-CCAT is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 166924.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0677 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.1792-12_1792-10dupATG		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.1828-12_1828-10dupATG		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.1675-12_1675-10dupATG		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.1792-10_1792-9insATG		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.1444-10_1444-9insATG		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000635193.1	TSL:1	n.1108-10_1108-9insATG		intron	N/A	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3313 AN: 150378 Hom.: 100 Cov.: 0

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.00332

Gnomad AMR AF: 0.00885

Gnomad ASJ AF: 0.00840

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00485

Gnomad FIN AF: 0.00136

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00336

Gnomad OTH AF: 0.0126

GnomAD2 exomes AF: 0.00964 AC: 1882 AN: 195300 AF XY: 0.00837

Gnomad AFR exome AF: 0.0755

Gnomad AMR exome AF: 0.00471

Gnomad ASJ exome AF: 0.00929

Gnomad EAS exome AF: 0.0000809

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00470

Gnomad OTH exome AF: 0.00657

GnomAD4 exome AF: 0.00565 AC: 7732 AN: 1368102 Hom.: 53 Cov.: 0 AF XY: 0.00548 AC XY: 3736 AN XY: 681576

African (AFR) AF: 0.0711 AC: 2306 AN: 32452

American (AMR) AF: 0.00422 AC: 178 AN: 42210

Ashkenazi Jewish (ASJ) AF: 0.00802 AC: 200 AN: 24946

East Asian (EAS) AF: 0.0000547 AC: 2 AN: 36554

South Asian (SAS) AF: 0.00565 AC: 458 AN: 81064

European-Finnish (FIN) AF: 0.00115 AC: 59 AN: 51118

Middle Eastern (MID) AF: 0.00487 AC: 27 AN: 5540

European-Non Finnish (NFE) AF: 0.00391 AC: 4054 AN: 1037568

Other (OTH) AF: 0.00791 AC: 448 AN: 56650

GnomAD4 genome AF: 0.0220 AC: 3318 AN: 150492 Hom.: 100 Cov.: 0 AF XY: 0.0215 AC XY: 1574 AN XY: 73358

African (AFR) AF: 0.0698 AC: 2861 AN: 40986

American (AMR) AF: 0.00883 AC: 133 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.00840 AC: 29 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5056

South Asian (SAS) AF: 0.00486 AC: 23 AN: 4736

European-Finnish (FIN) AF: 0.00136 AC: 14 AN: 10294

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00337 AC: 228 AN: 67632

Other (OTH) AF: 0.0125 AC: 26 AN: 2082

Alfa AF: 0.00487 Hom.: 3593

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	4	not provided (5)
-	-	2	not specified (2)
-	-	1	Connective tissue disorder (1)
-	1	-	Fibrochondrogenesis 1 (1)
-	1	-	Marshall syndrome (1)
-	1	-	Stickler Syndrome, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.17
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;