chr20-62836546-G-C

Variant names:

• chr20-62836546-G-C
• rs910152
• NM_001853.4:c.1603+14G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001853.4(COL9A3):​c.1603+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 1,603,554 control chromosomes in the GnomAD database, including 653,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (63991 hom., cov: 34)
  • Exomes 𝑓: 0.90 (589022 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.929
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• epiphyseal dysplasia, multiple, 3

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Stickler syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Ambry Genetics, Genomics England PanelApp
• Stickler syndrome, type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• multiple epiphyseal dysplasia due to collagen 9 anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive Stickler syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 20-62836546-G-C is Benign according to our data. Variant chr20-62836546-G-C is described in ClinVar as Benign. ClinVar VariationId is 258415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001853.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	NM_001853.4	MANE Select	c.1603+14G>C		intron	N/A	NP_001844.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	ENST00000649368.1	MANE Select	c.1603+14G>C		intron	N/A	ENSP00000496793.1	Q14050
	COL9A3	ENST00000467819.5	TSL:1	n.114+14G>C		intron	N/A
	COL9A3	ENST00000934236.1		c.1654+14G>C		intron	N/A	ENSP00000604295.1

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139389 AN: 152126 Hom.: 63940 Cov.: 34

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.896

GnomAD2 exomes AF: 0.920 AC: 212212 AN: 230572 AF XY: 0.920

Gnomad AFR exome AF: 0.944

Gnomad AMR exome AF: 0.946

Gnomad ASJ exome AF: 0.950

Gnomad EAS exome AF: 0.943

Gnomad FIN exome AF: 0.924

Gnomad NFE exome AF: 0.893

Gnomad OTH exome AF: 0.906

GnomAD4 exome AF: 0.900 AC: 1306898 AN: 1451310 Hom.: 589022 Cov.: 47 AF XY: 0.902 AC XY: 650030 AN XY: 720812

African (AFR) AF: 0.945 AC: 31552 AN: 33374

American (AMR) AF: 0.942 AC: 40616 AN: 43132

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 24448 AN: 25866

East Asian (EAS) AF: 0.955 AC: 37547 AN: 39324

South Asian (SAS) AF: 0.954 AC: 81151 AN: 85038

European-Finnish (FIN) AF: 0.925 AC: 48316 AN: 52238

Middle Eastern (MID) AF: 0.923 AC: 5306 AN: 5750

European-Non Finnish (NFE) AF: 0.889 AC: 983632 AN: 1106680

Other (OTH) AF: 0.907 AC: 54330 AN: 59908

GnomAD4 genome AF: 0.916 AC: 139500 AN: 152244 Hom.: 63991 Cov.: 34 AF XY: 0.919 AC XY: 68362 AN XY: 74416

African (AFR) AF: 0.943 AC: 39177 AN: 41540

American (AMR) AF: 0.910 AC: 13926 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 3293 AN: 3470

East Asian (EAS) AF: 0.943 AC: 4881 AN: 5178

South Asian (SAS) AF: 0.954 AC: 4607 AN: 4828

European-Finnish (FIN) AF: 0.930 AC: 9869 AN: 10612

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60744 AN: 67990

Other (OTH) AF: 0.897 AC: 1895 AN: 2112

Alfa AF: 0.905 Hom.: 6785

Bravo AF: 0.916

Asia WGS AF: 0.953 AC: 3311 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.56
DANN	Benign	0.24
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs910152; hg19: chr20-61467898;