rs116108376

chr20-62840741-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001853.4(COL9A3):c.*9G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,558,860 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (29 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (22 hom.)
• Consequence: COL9A3 NM_001853.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.644

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 20-62840741-G-A is Benign according to our data. Variant chr20-62840741-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00921 (1403/152316) while in subpopulation AFR AF= 0.0323 (1342/41580). AF 95% confidence interval is 0.0308. There are 29 homozygotes in gnomad4. There are 671 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.*9G>A		3_prime_UTR_variant	32/32	ENST00000649368.1
COL9A3	XM_047439893.1	c.*9G>A		3_prime_UTR_variant	31/31
COL9A3	XM_047439894.1	c.*9G>A		3_prime_UTR_variant	32/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.*9G>A		3_prime_UTR_variant	32/32		NM_001853.4	P1
COL9A3	ENST00000467819.5	n.575G>A		non_coding_transcript_exon_variant	4/4	1
COL9A3	ENST00000462700.5	n.819G>A		non_coding_transcript_exon_variant	6/6	3
COL9A3	ENST00000466192.5	n.1791G>A		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.00917 AC: 1396 AN: 152198 Hom.: 29 Cov.: 33

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00238 AC: 388 AN: 162976 Hom.: 5 AF XY: 0.00163 AC XY: 141 AN XY: 86240

Gnomad AFR exome AF: 0.0356

Gnomad AMR exome AF: 0.00175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000166

Gnomad SAS exome AF: 0.0000429

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000311

Gnomad OTH exome AF: 0.000664

GnomAD4 exome AF: 0.000951 AC: 1338 AN: 1406544 Hom.: 22 Cov.: 32 AF XY: 0.000795 AC XY: 552 AN XY: 694450

Gnomad4 AFR exome AF: 0.0355

Gnomad4 AMR exome AF: 0.00166

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000137

Gnomad4 SAS exome AF: 0.000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000139

Gnomad4 OTH exome AF: 0.00175

GnomAD4 genome AF: 0.00921 AC: 1403 AN: 152316 Hom.: 29 Cov.: 33 AF XY: 0.00901 AC XY: 671 AN XY: 74488

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00468 Hom.: 4

Bravo AF: 0.0101

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 03, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.14
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs116108376; hg19: chr20-61472093;