Variant 6-70253453-T-G 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.1720-24A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,568,784 control chromosomes in the GnomAD database, including 130,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13531 hom., cov: 32)

Exomes 𝑓: 0.40 ( 116522 hom. )

Consequence

COL9A1
NM_001851.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.722

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:

COL9A1 (HGNC:):

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=-0.92).

BP6

Variant 6-70253453-T-G is Benign according to our data. Variant chr6-70253453-T-G is described in ClinVar as [Benign]. Clinvar id is 258350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A1	NM_001851.6 linkuse as main transcript	c.1720-24A>C		intron_variant		ENST00000357250.11	NP_001842.3	P20849-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A1	ENST00000357250.11 linkuse as main transcript	c.1720-24A>C		intron_variant		1	NM_001851.6	ENSP00000349790.6		P20849-1

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63507

AN:

151906

Hom.:

13527

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.395

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.399

GnomAD3 exomes

AF:

0.382

AC:

95799

AN:

250958

Hom.:

18882

AF XY:

0.381

AC XY:

51648

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.496

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.436

Gnomad EAS exome

AF:

0.283

Gnomad SAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.420

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.402

AC:

569817

AN:

1416760

Hom.:

116522

Cov.:

AF XY:

0.399

AC XY:

282337

AN XY:

707572

show subpopulations

Gnomad4 AFR exome

AF:

0.495

Gnomad4 AMR exome

AF:

0.304

Gnomad4 ASJ exome

AF:

0.429

Gnomad4 EAS exome

AF:

0.271

Gnomad4 SAS exome

AF:

0.308

Gnomad4 FIN exome

AF:

0.394

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.418

AC:

63550

AN:

152024

Hom.:

13531

Cov.:

AF XY:

0.412

AC XY:

30635

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.489

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.431

Gnomad4 EAS

AF:

0.282

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.395

Gnomad4 NFE

AF:

0.416

Gnomad4 OTH

AF:

0.398

Alfa

AF:

0.331

Hom.:

1378

Bravo

AF:

0.421

Asia WGS

AF:

0.302

AC:

1052

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

-0.92

CADD

Benign

1.2

DANN

Benign

0.44

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