dbSNP rs117347229: COL9A3:c.346-22G>A (chr20-62821485-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.346-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,612,528 control chromosomes in the GnomAD database, including 8,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.086 ( 678 hom., cov: 33)

Exomes 𝑓: 0.10 ( 7940 hom. )

Consequence

COL9A3
NM_001853.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.09

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

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 20-62821485-G-A is Benign according to our data. Variant chr20-62821485-G-A is described in ClinVar as [Benign]. Clinvar id is 258423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.346-22G>A		intron_variant	Intron 6 of 31	ENST00000649368.1	NP_001844.3	Q14050

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL9A3	ENST00000649368.1 link	c.346-22G>A	intron_variant	Intron 6 of 31		NM_001853.4	ENSP00000496793.1	Q14050
COL9A3	ENST00000452372.2 link	c.235-22G>A	intron_variant	Intron 5 of 11	5		ENSP00000394280.1	Q4VXW1
COL9A3	ENST00000477612.5 link	n.342-22G>A	intron_variant	Intron 6 of 11	3
COL9A3	ENST00000489045.5 link	n.392-22G>A	intron_variant	Intron 5 of 13	5

Frequencies

GnomAD3 genomes

AF:

0.0863

AC:

13125

AN:

152088

Hom.:

680

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0457

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.0791

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0975

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.0974

GnomAD3 exomes

AF:

0.0910

AC:

22757

AN:

249952

Hom.:

1228

AF XY:

0.0968

AC XY:

13131

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.0437

Gnomad AMR exome

AF:

0.0589

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.00479

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0939

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.100

AC:

146200

AN:

1460322

Hom.:

7940

Cov.:

AF XY:

0.102

AC XY:

73987

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.0455

Gnomad4 AMR exome

AF:

0.0614

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.00307

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0956

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.0962

GnomAD4 genome

AF:

0.0862

AC:

13113

AN:

152206

Hom.:

678

Cov.:

AF XY:

0.0864

AC XY:

6430

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0455

Gnomad4 AMR

AF:

0.0790

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.00271

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0975

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.0959

Alfa

AF:

0.0966

Hom.:

140

Bravo

AF:

0.0804

Asia WGS

AF:

0.0600

AC:

210

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

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.54

CADD

Benign

DANN

Benign

0.81

BranchPoint Hunter

4.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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