Variant chr6-70216631-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.*266T>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 0.39 in 483,742 control chromosomes in the GnomAD database, including 38,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 12629 hom., cov: 31)

Exomes 𝑓: 0.38 ( 26115 hom. )

Consequence

COL9A1
NM_001851.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.733

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=-0.82).

BP6

Variant 6-70216631-A-G is Benign according to our data. Variant chr6-70216631-A-G is described in ClinVar as [Benign]. Clinvar id is 1271891.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 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.*266T>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.*266T>C		3_prime_UTR_variant	38/38	1	NM_001851.6	P1	P20849-1

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61254

AN:

150504

Hom.:

12606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.400

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.549

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.423

GnomAD4 exome

AF:

0.382

AC:

127279

AN:

333122

Hom.:

26115

Cov.:

AF XY:

0.384

AC XY:

67606

AN XY:

175988

show subpopulations

Gnomad4 AFR exome

AF:

0.436

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.550

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.412

Gnomad4 FIN exome

AF:

0.323

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.398

GnomAD4 genome

AF:

0.407

AC:

61308

AN:

150620

Hom.:

12629

Cov.:

AF XY:

0.401

AC XY:

29451

AN XY:

73428

show subpopulations

Gnomad4 AFR

AF:

0.453

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.549

Gnomad4 EAS

AF:

0.226

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.395

Gnomad4 OTH

AF:

0.422

Alfa

AF:

0.406

Hom.:

12685

Bravo

AF:

0.409

Asia WGS

AF:

0.306

AC:

1069

AN:

3478

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 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.0

DANN

Benign

0.57

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