Variant 6-70216668-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001851.6(COL9A1):c.*229T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 506,042 control chromosomes in the GnomAD database, including 1,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.099 ( 998 hom., cov: 31)

Exomes 𝑓: 0.051 ( 697 hom. )

Consequence

COL9A1
NM_001851.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.98

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-70216668-A-G is Benign according to our data. Variant chr6-70216668-A-G is described in ClinVar as [Benign]. Clinvar id is 1230709.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-70216668-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 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.*229T>C		3_prime_UTR_variant	38/38	ENST00000357250.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A1	ENST00000357250.11 linkuse as main transcript	c.*229T>C		3_prime_UTR_variant	38/38	1	NM_001851.6	P1	P20849-1

Frequencies

GnomAD3 genomes

AF:

0.0994

AC:

14039

AN:

141236

Hom.:

999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.0213

Gnomad AMR

AF:

0.0591

Gnomad ASJ

AF:

0.0386

Gnomad EAS

AF:

0.00577

Gnomad SAS

AF:

0.0530

Gnomad FIN

AF:

0.0587

Gnomad MID

AF:

0.0227

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.0760

GnomAD4 exome

AF:

0.0511

AC:

18642

AN:

364712

Hom.:

697

Cov.:

AF XY:

0.0501

AC XY:

9589

AN XY:

191560

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.0388

Gnomad4 ASJ exome

AF:

0.0294

Gnomad4 EAS exome

AF:

0.00203

Gnomad4 SAS exome

AF:

0.0438

Gnomad4 FIN exome

AF:

0.0475

Gnomad4 NFE exome

AF:

0.0533

Gnomad4 OTH exome

AF:

0.0561

GnomAD4 genome

AF:

0.0994

AC:

14042

AN:

141330

Hom.:

998

Cov.:

AF XY:

0.0984

AC XY:

6756

AN XY:

68630

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.0590

Gnomad4 ASJ

AF:

0.0386

Gnomad4 EAS

AF:

0.00578

Gnomad4 SAS

AF:

0.0531

Gnomad4 FIN

AF:

0.0587

Gnomad4 NFE

AF:

0.0637

Gnomad4 OTH

AF:

0.0751

Alfa

AF:

0.0373

Hom.:

Bravo

AF:

0.0980

Asia WGS

AF:

0.0260

AC:

AN:

3450

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.094

DANN

Benign

0.51

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