Genetic Variant COL11A1:c.1792-15_1792-10dupATGATG (chr1-103005900-C-CCATCAT) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS1

The NM_001854.4(COL11A1):c.1792-15_1792-10dupATGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00072 ( 1 hom., cov: 0)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

COL11A1
NM_001854.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:2

Conservation

PhyloP100: -0.166

Variant links:

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]

COL11A1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 1-103005900-C-CCATCAT is Benign according to our data. Variant chr1-103005900-C-CCATCAT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 291530.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=3}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000724 (109/150510) while in subpopulation AFR AF= 0.00256 (105/40998). AF 95% confidence interval is 0.00216. There are 1 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4 link	c.1792-15_1792-10dupATGATG		intron_variant	Intron 17 of 66	ENST00000370096.9	NP_001845.3	P12107-1Q59HB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9 link	c.1792-10_1792-9insATGATG		intron_variant	Intron 17 of 66	1	NM_001854.4	ENSP00000359114.3		P12107-1

Frequencies

GnomAD3 genomes

AF:

0.000718

AC:

108

AN:

150396

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000220

AC:

AN:

195300

Hom.:

AF XY:

0.000181

AC XY:

AN XY:

105128

show subpopulations

Gnomad AFR exome

AF:

0.00305

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000760

AC:

104

AN:

1368180

Hom.:

Cov.:

AF XY:

0.0000704

AC XY:

AN XY:

681606

show subpopulations

Gnomad4 AFR exome

AF:

0.00271

Gnomad4 AMR exome

AF:

0.0000474

Gnomad4 ASJ exome

AF:

0.0000401

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000482

Gnomad4 OTH exome

AF:

0.000124

GnomAD4 genome

AF:

0.000724

AC:

109

AN:

150510

Hom.:

Cov.:

AF XY:

0.000695

AC XY:

AN XY:

73366

show subpopulations

Gnomad4 AFR

AF:

0.00256

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Marshall syndrome

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibrochondrogenesis 1

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Stickler Syndrome, Dominant

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

1-103005900-CCATCATCATCATCATCAT-CCATCATCATCATCATCATCATCAT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over