dbSNP rs633762: COL9A1:c.1504-32T>G (chr6-70255422-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001851.6(COL9A1):c.1504-32T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,596,956 control chromosomes in the GnomAD database, including 501,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54117 hom., cov: 32)

Exomes 𝑓: 0.79 ( 447171 hom. )

Consequence

COL9A1
NM_001851.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.130

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 6-70255422-A-C is Benign according to our data. Variant chr6-70255422-A-C is described in ClinVar as [Benign]. Clinvar id is 258344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A1	NM_001851.6 link	c.1504-32T>G		intron_variant	Intron 21 of 37	ENST00000357250.11	NP_001842.3	P20849-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A1	ENST00000357250.11 link	c.1504-32T>G		intron_variant	Intron 21 of 37	1	NM_001851.6	ENSP00000349790.6		P20849-1

Frequencies

GnomAD3 genomes

AF:

0.838

AC:

127544

AN:

152130

Hom.:

54044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.959

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.849

Gnomad ASJ

AF:

0.827

Gnomad EAS

AF:

0.930

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.777

Gnomad OTH

AF:

0.811

GnomAD3 exomes

AF:

0.810

AC:

202980

AN:

250650

Hom.:

82805

AF XY:

0.800

AC XY:

108424

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.967

Gnomad AMR exome

AF:

0.881

Gnomad ASJ exome

AF:

0.831

Gnomad EAS exome

AF:

0.921

Gnomad SAS exome

AF:

0.756

Gnomad FIN exome

AF:

0.747

Gnomad NFE exome

AF:

0.773

Gnomad OTH exome

AF:

0.797

GnomAD4 exome

AF:

0.785

AC:

1134633

AN:

1444708

Hom.:

447171

Cov.:

AF XY:

0.783

AC XY:

563613

AN XY:

719836

show subpopulations

Gnomad4 AFR exome

AF:

0.967

Gnomad4 AMR exome

AF:

0.876

Gnomad4 ASJ exome

AF:

0.824

Gnomad4 EAS exome

AF:

0.939

Gnomad4 SAS exome

AF:

0.754

Gnomad4 FIN exome

AF:

0.748

Gnomad4 NFE exome

AF:

0.773

Gnomad4 OTH exome

AF:

0.799

GnomAD4 genome

AF:

0.839

AC:

127677

AN:

152248

Hom.:

54117

Cov.:

AF XY:

0.837

AC XY:

62302

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.959

Gnomad4 AMR

AF:

0.849

Gnomad4 ASJ

AF:

0.827

Gnomad4 EAS

AF:

0.930

Gnomad4 SAS

AF:

0.769

Gnomad4 FIN

AF:

0.752

Gnomad4 NFE

AF:

0.777

Gnomad4 OTH

AF:

0.814

Alfa

AF:

0.781

Hom.:

19493

Bravo

AF:

0.852

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Epiphyseal dysplasia, multiple, 6

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.5

DANN

Benign

0.29

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