rs201491791

Positions:

• chr1-102914421-G-A
• chr1-102914421-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001854.4(COL11A1):​c.3925-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,591,884 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (7 hom.)
• Consequence: COL11A1 NM_001854.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.523

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=-0.85).
• BP6: Variant 1-102914421-G-A is Benign according to our data. Variant chr1-102914421-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 379418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-102914421-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00105 (160/151924) while in subpopulation SAS AF= 0.00208 (10/4808). AF 95% confidence interval is 0.00128. There are 0 homozygotes in gnomad4. There are 83 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.3925-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.3925-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001854.4	P1

Frequencies

GnomAD3 genomes AF: 0.00105 AC: 159 AN: 151806 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0000951

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00152

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00128 AC: 309 AN: 241234 Hom.: 1 AF XY: 0.00142 AC XY: 186 AN XY: 131138

Gnomad AFR exome AF: 0.000330

Gnomad AMR exome AF: 0.000386

Gnomad ASJ exome AF: 0.00234

Gnomad EAS exome AF: 0.0000567

Gnomad SAS exome AF: 0.00305

Gnomad FIN exome AF: 0.000376

Gnomad NFE exome AF: 0.00141

Gnomad OTH exome AF: 0.00272

GnomAD4 exome AF: 0.00141 AC: 2037 AN: 1439960 Hom.: 7 Cov.: 31 AF XY: 0.00148 AC XY: 1061 AN XY: 716198

Gnomad4 AFR exome AF: 0.0000911

Gnomad4 AMR exome AF: 0.000501

Gnomad4 ASJ exome AF: 0.00271

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00304

Gnomad4 FIN exome AF: 0.000379

Gnomad4 NFE exome AF: 0.00137

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00105 AC: 160 AN: 151924 Hom.: 0 Cov.: 32 AF XY: 0.00112 AC XY: 83 AN XY: 74240

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.0000951

Gnomad4 NFE AF: 0.00152

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000970 Hom.: 0

Bravo AF: 0.000933

Asia WGS AF: 0.00202 AC: 7 AN: 3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 20, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 28, 2017

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. -

Connective tissue disorder Benign:1

Likely benign, 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
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.12
DANN	Benign	0.43

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: rs201491791; hg19: chr1-103379977;