rs1252968708

Positions:

• chr1-102987655-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001854.4(COL11A1):​c.2480C>T​(p.Pro827Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COL11A1 NM_001854.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3944674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL11A1	NM_001854.4	c.2480C>T	p.Pro827Leu	missense_variant	30/67	ENST00000370096.9	NP_001845.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9	c.2480C>T	p.Pro827Leu	missense_variant	30/67	1	NM_001854.4	ENSP00000359114	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461320 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726964

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Connective tissue disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Nov 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;.;.;.
Eigen	Benign	-0.079
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Benign	1.3	L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-6.9	D;D;D;D
REVEL	Uncertain	0.43
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.065	T;T;T;T
Polyphen		0.041	B;B;B;.
Vest4		0.28
MutPred		0.35		Gain of catalytic residue at P827 (P = 0.0916);.;.;.;
MVP		0.72
MPC		0.12
ClinPred		0.45	T
GERP RS		3.4
Varity_R		0.25
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1252968708; hg19: chr1-103453211; COSMIC: COSV105259704;