6-70216631-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.733

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]

ACMG classification

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	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	c.*266T>C		3_prime_UTR_variant	38/38	1	NM_001851.6	P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61254 AN: 150504 Hom.: 12606 Cov.: 31

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.: 2 AF XY: 0.384 AC XY: 67606 AN XY: 175988

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.: 31 AF XY: 0.401 AC XY: 29451 AN XY: 73428

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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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

Other links and lift over

dbSNP: rs1064250; hg19: chr6-70926334; COSMIC: COSV57893021; COSMIC: COSV57893021;