rs143159512

Positions:

• chr1-103082940-A-G
• chr1-103082940-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001854.4(COL11A1):​c.139T>C​(p.Phe47Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F47I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL11A1 NM_001854.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.36

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.139T>C	p.Phe47Leu	missense_variant	2/67	ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.139T>C	p.Phe47Leu	missense_variant	2/67	1	NM_001854.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.36	T;.;.;.;.;.;.;.;.
Eigen	Benign	0.083
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.52	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;L;L;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.1	N;N;N;N;.;.;.;.;D
REVEL	Benign	0.18
Sift	Benign	0.37	T;T;T;T;.;.;.;.;T
Sift4G	Benign	0.58	T;T;T;T;.;.;.;.;.
Polyphen		0.12	B;B;B;.;.;.;.;.;.
Vest4		0.45
MutPred		0.63		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.22
MPC		0.61
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.26
gMVP		0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs143159512; hg19: chr1-103548496; COSMIC: COSV100616355; COSMIC: COSV100616355;