rs495823

Variant names:

• chr6-70286887-G-A
• rs495823
• NM_001851.6:c.697-3067C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-70286887-G-A
• chr6-70286887-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001851.6(COL9A1):​c.697-3067C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,102 control chromosomes in the GnomAD database, including 26,687 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26687 hom., cov: 32)
• Consequence: COL9A1 NM_001851.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• epiphyseal dysplasia, multiple, 6

  Inheritance: AD, AR, Unknown Classification: DEFINITIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Stickler syndrome, type 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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
• Stickler syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A1	NM_001851.6	c.697-3067C>T		intron_variant	Intron 5 of 37	ENST00000357250.11	NP_001842.3
COL9A1	NM_001377291.1	c.697-3067C>T		intron_variant	Intron 5 of 10		NP_001364220.1
COL9A1	XM_011535429.4	c.697-3067C>T		intron_variant	Intron 5 of 38		XP_011533731.1
COL9A1	XM_017010246.3	c.148-3067C>T		intron_variant	Intron 2 of 35		XP_016865735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A1	ENST00000357250.11	c.697-3067C>T		intron_variant	Intron 5 of 37	1	NM_001851.6	ENSP00000349790.6
COL9A1	ENST00000370496.3	c.697-3067C>T		intron_variant	Intron 5 of 10	1		ENSP00000359527.3

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88431 AN: 151984 Hom.: 26629 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.579

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.582 AC: 88551 AN: 152102 Hom.: 26687 Cov.: 32 AF XY: 0.586 AC XY: 43585 AN XY: 74342

African (AFR) AF: 0.665 AC: 27590 AN: 41508

American (AMR) AF: 0.683 AC: 10445 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1942 AN: 3468

East Asian (EAS) AF: 0.960 AC: 4977 AN: 5186

South Asian (SAS) AF: 0.663 AC: 3200 AN: 4826

European-Finnish (FIN) AF: 0.441 AC: 4655 AN: 10552

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33905 AN: 67958

Other (OTH) AF: 0.584 AC: 1235 AN: 2114

Alfa AF: 0.528 Hom.: 29402

Bravo AF: 0.604

Asia WGS AF: 0.820 AC: 2850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.94
DANN	Benign	0.59
PhyloP100		-0.41
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: rs495823; hg19: chr6-70996590;