rs12143740

Variant names:

• chr1-102944507-A-G
• rs12143740
• NM_001854.4:c.3276+2342T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001854.4(COL11A1):​c.3276+2342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,112 control chromosomes in the GnomAD database, including 2,083 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2083 hom., cov: 32)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 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.3276+2342T>C		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.3312+2342T>C		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.3159+2342T>C		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.3276+2342T>C		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.2928+2342T>C		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000635193.1	TSL:1	n.*526+2342T>C		intron	N/A	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22977 AN: 151994 Hom.: 2084 Cov.: 32

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.151 AC: 22977 AN: 152112 Hom.: 2083 Cov.: 32 AF XY: 0.154 AC XY: 11476 AN XY: 74370

African (AFR) AF: 0.0499 AC: 2073 AN: 41566

American (AMR) AF: 0.186 AC: 2835 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3470

East Asian (EAS) AF: 0.115 AC: 596 AN: 5180

South Asian (SAS) AF: 0.188 AC: 908 AN: 4822

European-Finnish (FIN) AF: 0.221 AC: 2343 AN: 10578

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12886 AN: 67916

Other (OTH) AF: 0.153 AC: 323 AN: 2114

Alfa AF: 0.169 Hom.: 327

Bravo AF: 0.143

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.65
PhyloP100		0.029
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: rs12143740; hg19: chr1-103410063;