Variant rs519068 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001851.6(COL9A1):c.1765-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,606,610 control chromosomes in the GnomAD database, including 186,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17648 hom., cov: 32)

Exomes 𝑓: 0.48 ( 169237 hom. )

Consequence

COL9A1
NM_001851.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.243

Variant links:

Genes affected

COL9A1 (HGNC:2217): (collagen type IX alpha 1 chain) This gene encodes one of the three alpha chains of type IX collagen, which is a minor (5-20%) collagen component of hyaline cartilage. Type IX collagen is usually found in tissues containing type II collagen, a fibrillar collagen. Studies in knockout mice have shown that synthesis of the alpha 1 chain is essential for assembly of type IX collagen molecules, a heterotrimeric molecule, and that lack of type IX collagen is associated with early onset osteoarthritis. Mutations in this gene are associated with osteoarthritis in humans, with multiple epiphyseal dysplasia, 6, a form of chondrodysplasia, and with Stickler syndrome, a disease characterized by ophthalmic, orofacial, articular, and auditory defects. Two transcript variants that encode different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

COL9A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-70252341-A-G is Benign according to our data. Variant chr6-70252341-A-G is described in ClinVar as [Benign]. Clinvar id is 258352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A1	NM_001851.6 linkuse as main transcript	c.1765-26T>C		intron_variant		ENST00000357250.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A1	ENST00000357250.11 linkuse as main transcript	c.1765-26T>C		intron_variant		1	NM_001851.6	P1	P20849-1

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72445

AN:

151912

Hom.:

17629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.485

Gnomad EAS

AF:

0.289

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.441

AC:

110556

AN:

250532

Hom.:

25340

AF XY:

0.442

AC XY:

59833

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.522

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.484

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.500

Gnomad OTH exome

AF:

0.452

GnomAD4 exome

AF:

0.478

AC:

695932

AN:

1454580

Hom.:

169237

Cov.:

AF XY:

0.475

AC XY:

343983

AN XY:

724134

show subpopulations

Gnomad4 AFR exome

AF:

0.518

Gnomad4 AMR exome

AF:

0.331

Gnomad4 ASJ exome

AF:

0.481

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.481

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.466

GnomAD4 genome

AF:

0.477

AC:

72509

AN:

152030

Hom.:

17648

Cov.:

AF XY:

0.471

AC XY:

34985

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.518

Gnomad4 AMR

AF:

0.375

Gnomad4 ASJ

AF:

0.485

Gnomad4 EAS

AF:

0.287

Gnomad4 SAS

AF:

0.353

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.500

Gnomad4 OTH

AF:

0.445

Alfa

AF:

0.485

Hom.:

18763

Bravo

AF:

0.474

Asia WGS

AF:

0.332

AC:

1155

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Epiphyseal dysplasia, multiple, 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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

-0.83

CADD

Benign

6.8

DANN

Benign

0.66

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

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

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