dbSNP rs36094661: COL9A3:c.631-45G>A (chr20-62825772-G-A) – 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_001853.4(COL9A3):c.631-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,545,894 control chromosomes in the GnomAD database, including 19,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1348 hom., cov: 34)

Exomes 𝑓: 0.16 ( 18415 hom. )

Consequence

COL9A3
NM_001853.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.837

Variant links:

Genes affected

COL9A3 (HGNC:2219): (collagen type IX alpha 3 chain) This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. Mutations in this gene are associated with multiple epiphyseal dysplasia type 3. [provided by RefSeq, Jan 2010]

COL9A3 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=-0.84).

BP6

Variant 20-62825772-G-A is Benign according to our data. Variant chr20-62825772-G-A is described in ClinVar as [Benign]. Clinvar id is 258429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.631-45G>A		intron_variant	Intron 12 of 31	ENST00000649368.1	NP_001844.3	Q14050

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL9A3	ENST00000649368.1 link	c.631-45G>A	intron_variant	Intron 12 of 31		NM_001853.4	ENSP00000496793.1	Q14050
COL9A3	ENST00000452372.2 link	c.520-45G>A	intron_variant	Intron 11 of 11	5		ENSP00000394280.1	Q4VXW1
COL9A3	ENST00000463487.2 link	n.339-45G>A	intron_variant	Intron 4 of 10	5
COL9A3	ENST00000489045.5 link	n.677-45G>A	intron_variant	Intron 11 of 13	5

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18777

AN:

152170

Hom.:

1349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0569

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0987

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.0364

Gnomad SAS

AF:

0.0740

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.122

AC:

19065

AN:

156332

Hom.:

1483

AF XY:

0.122

AC XY:

10031

AN XY:

82334

show subpopulations

Gnomad AFR exome

AF:

0.0602

Gnomad AMR exome

AF:

0.0697

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.0346

Gnomad SAS exome

AF:

0.0714

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.156

AC:

218046

AN:

1393606

Hom.:

18415

Cov.:

AF XY:

0.154

AC XY:

106229

AN XY:

687722

show subpopulations

Gnomad4 AFR exome

AF:

0.0533

Gnomad4 AMR exome

AF:

0.0730

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.0290

Gnomad4 SAS exome

AF:

0.0727

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.173

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.123

AC:

18773

AN:

152288

Hom.:

1348

Cov.:

AF XY:

0.122

AC XY:

9087

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0568

Gnomad4 AMR

AF:

0.0987

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.0361

Gnomad4 SAS

AF:

0.0743

Gnomad4 FIN

AF:

0.194

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.138

Hom.:

283

Bravo

AF:

0.114

Asia WGS

AF:

0.0490

AC:

172

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.84

CADD

Benign

0.77

DANN

Benign

0.85

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