1-103005900-CCATCATCATCATCATCAT-CCATCATCATCATCAT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001854.4(COL11A1):​c.1792-12_1792-10delATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 1,517,264 control chromosomes in the GnomAD database, including 434,303 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46376 hom., cov: 0)
  • Exomes 𝑓: 0.77 (387927 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.23
• 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 -16 ACMG points.

• BP6: Variant 1-103005900-CCAT-C is Benign according to our data. Variant chr1-103005900-CCAT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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_1792-10delATG		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.1828-12_1828-10delATG		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.1675-12_1675-10delATG		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.1792-12_1792-10delATG		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.1444-12_1444-10delATG		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000635193.1	TSL:1	n.1108-12_1108-10delATG		intron	N/A	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes AF: 0.775 AC: 116445 AN: 150312 Hom.: 46344 Cov.: 0

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.792

GnomAD2 exomes AF: 0.804 AC: 157046 AN: 195300 AF XY: 0.806

Gnomad AFR exome AF: 0.525

Gnomad AMR exome AF: 0.896

Gnomad ASJ exome AF: 0.706

Gnomad EAS exome AF: 0.992

Gnomad FIN exome AF: 0.799

Gnomad NFE exome AF: 0.804

Gnomad OTH exome AF: 0.794

GnomAD4 exome AF: 0.770 AC: 1052443 AN: 1366840 Hom.: 387927 AF XY: 0.770 AC XY: 524328 AN XY: 680926

African (AFR) AF: 0.520 AC: 16787 AN: 32282

American (AMR) AF: 0.825 AC: 34794 AN: 42182

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 17041 AN: 24866

East Asian (EAS) AF: 0.890 AC: 32543 AN: 36554

South Asian (SAS) AF: 0.761 AC: 61601 AN: 80946

European-Finnish (FIN) AF: 0.763 AC: 38920 AN: 51032

Middle Eastern (MID) AF: 0.770 AC: 4256 AN: 5530

European-Non Finnish (NFE) AF: 0.775 AC: 803731 AN: 1036862

Other (OTH) AF: 0.756 AC: 42770 AN: 56586

GnomAD4 genome AF: 0.775 AC: 116528 AN: 150424 Hom.: 46376 Cov.: 0 AF XY: 0.777 AC XY: 56958 AN XY: 73338

African (AFR) AF: 0.571 AC: 23403 AN: 40956

American (AMR) AF: 0.872 AC: 13122 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2625 AN: 3450

East Asian (EAS) AF: 0.994 AC: 5027 AN: 5056

South Asian (SAS) AF: 0.869 AC: 4112 AN: 4734

European-Finnish (FIN) AF: 0.812 AC: 8351 AN: 10288

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57320 AN: 67608

Other (OTH) AF: 0.794 AC: 1654 AN: 2082

Alfa AF: 0.721 Hom.: 3593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Fibrochondrogenesis 1 (1)
-	-	1	Hearing loss, autosomal dominant 37 (1)
-	-	1	Marshall syndrome (1)
-	-	1	Stickler syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
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: rs71752747; hg19: chr1-103471456; COSMIC: COSV106062260; COSMIC: COSV106062260;