rs6668897

chr1-103078635-C-T

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.488+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,598,358 control chromosomes in the GnomAD database, including 19,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1596 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17973 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0880

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 (BayesDel_noAF=-0.77).
• BP6: Variant 1-103078635-C-T is Benign according to our data. Variant chr1-103078635-C-T is described in ClinVar as [Benign]. Clinvar id is 258471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.488+23G>A		intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.488+23G>A		intron_variant		1	NM_001854.4	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20913 AN: 151816 Hom.: 1594 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.00890

Gnomad SAS AF: 0.0908

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.149 AC: 37255 AN: 250088 Hom.: 3137 AF XY: 0.147 AC XY: 19842 AN XY: 135268

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.00631

Gnomad SAS exome AF: 0.100

Gnomad FIN exome AF: 0.208

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.153 AC: 221820 AN: 1446424 Hom.: 17973 Cov.: 27 AF XY: 0.152 AC XY: 109760 AN XY: 720688

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.00692

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.138 AC: 20936 AN: 151934 Hom.: 1596 Cov.: 32 AF XY: 0.138 AC XY: 10280 AN XY: 74256

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.00892

Gnomad4 SAS AF: 0.0909

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.126

Alfa AF: 0.157 Hom.: 496

Bravo AF: 0.134

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	5.9
Dann	Benign	0.71

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: rs6668897; hg19: chr1-103544191;