rs12731843

Positions:

• chr1-103025905-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001854.4(COL11A1):​c.898-292A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 1,612,598 control chromosomes in the GnomAD database, including 3,701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (532 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3169 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0480

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017307997).
• BP6: Variant 1-103025905-T-G is Benign according to our data. Variant chr1-103025905-T-G is described in ClinVar as [Benign]. Clinvar id is 668356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-103025905-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.898-292A>C		intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.898-292A>C		intron_variant		1	NM_001854.4	P1

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 12002 AN: 152066 Hom.: 529 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0658

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0794

GnomAD3 exomes AF: 0.0706 AC: 17714 AN: 250762 Hom.: 716 AF XY: 0.0704 AC XY: 9554 AN XY: 135614

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.0546

Gnomad ASJ exome AF: 0.0821

Gnomad EAS exome AF: 0.0798

Gnomad SAS exome AF: 0.0680

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0615

Gnomad OTH exome AF: 0.0708

GnomAD4 exome AF: 0.0638 AC: 93242 AN: 1460414 Hom.: 3169 Cov.: 31 AF XY: 0.0638 AC XY: 46379 AN XY: 726624

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.0556

Gnomad4 ASJ exome AF: 0.0796

Gnomad4 EAS exome AF: 0.0641

Gnomad4 SAS exome AF: 0.0679

Gnomad4 FIN exome AF: 0.0990

Gnomad4 NFE exome AF: 0.0596

Gnomad4 OTH exome AF: 0.0706

GnomAD4 genome AF: 0.0791 AC: 12033 AN: 152184 Hom.: 532 Cov.: 32 AF XY: 0.0804 AC XY: 5982 AN XY: 74422

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0658

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.0725

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0591

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0654 Hom.: 413

Bravo AF: 0.0793

TwinsUK AF: 0.0547 AC: 203

ALSPAC AF: 0.0586 AC: 226

ESP6500AA AF: 0.112 AC: 493

ESP6500EA AF: 0.0636 AC: 547

ExAC AF: 0.0711 AC: 8635

Asia WGS AF: 0.0680 AC: 237 AN: 3478

EpiCase AF: 0.0643

EpiControl AF: 0.0634

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.95
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.16	T;T;T
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P
PROVEAN	Benign	-0.88	N;.;N
REVEL	Benign	0.094
Sift	Benign	0.45	T;.;T
Sift4G	Benign	0.40	T;.;.
Polyphen		0.0	B;.;.
Vest4		0.044
MutPred		0.34		Loss of methylation at K276 (P = 6e-04);.;Loss of methylation at K276 (P = 6e-04);
ClinPred		0.0097	T
GERP RS		0.88

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: rs12731843; hg19: chr1-103491461; COSMIC: COSV62181630; COSMIC: COSV62181630;