rs28648038

chr1-102914314-A-C

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.3978+38T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,484,264 control chromosomes in the GnomAD database, including 10,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (743 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9944 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.471

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=-0.88).
• BP6: Variant 1-102914314-A-C is Benign according to our data. Variant chr1-102914314-A-C is described in ClinVar as [Benign]. Clinvar id is 258462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.3978+38T>G		intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.3978+38T>G		intron_variant		1	NM_001854.4	P1

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13950 AN: 151878 Hom.: 740 Cov.: 32

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0980

GnomAD3 exomes AF: 0.0941 AC: 22618 AN: 240412 Hom.: 1246 AF XY: 0.0948 AC XY: 12323 AN XY: 130056

Gnomad AFR exome AF: 0.0548

Gnomad AMR exome AF: 0.0653

Gnomad ASJ exome AF: 0.0724

Gnomad EAS exome AF: 0.0114

Gnomad SAS exome AF: 0.0577

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.0984

GnomAD4 exome AF: 0.117 AC: 156201 AN: 1332268 Hom.: 9944 Cov.: 19 AF XY: 0.115 AC XY: 76974 AN XY: 668574

Gnomad4 AFR exome AF: 0.0540

Gnomad4 AMR exome AF: 0.0672

Gnomad4 ASJ exome AF: 0.0742

Gnomad4 EAS exome AF: 0.0124

Gnomad4 SAS exome AF: 0.0596

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0919 AC: 13965 AN: 151996 Hom.: 743 Cov.: 32 AF XY: 0.0922 AC XY: 6847 AN XY: 74268

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.0724

Gnomad4 ASJ AF: 0.0646

Gnomad4 EAS AF: 0.0149

Gnomad4 SAS AF: 0.0532

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0979

Alfa AF: 0.105 Hom.: 258

Bravo AF: 0.0877

Asia WGS AF: 0.0640 AC: 223 AN: 3476

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 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.20
Dann	Benign	0.45

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: rs28648038; hg19: chr1-103379870;