1-186296816-T-A

Variant summary

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

The NM_005807.6(PRG4):c.-30-30T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,219,838 control chromosomes in the GnomAD database, including 206,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (29481 hom., cov: 32)
  • Exomes 𝑓: 0.57 (177353 hom.)
• Consequence: PRG4 NM_005807.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.423

Genes affected

PRG4 (HGNC:9364): (proteoglycan 4) The protein encoded by this gene is a large proteoglycan that is synthesized by chondrocytes located at the surface of articular cartilage and by some synovial lining cells. This protein contains both chondroitin sulfate and keratan sulfate glycosaminoglycans. It functions as a boundary lubricant at the cartilage surface and contributes to the elastic absorption and energy dissipation of synovial fluid. Mutations in this gene result in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-186296816-T-A is Benign according to our data. Variant chr1-186296816-T-A is described in ClinVar as [Benign]. Clinvar id is 1327442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRG4	NM_005807.6	c.-30-30T>A		intron_variant		ENST00000445192.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRG4	ENST00000445192.7	c.-30-30T>A		intron_variant		5	NM_005807.6	P2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92966 AN: 151962 Hom.: 29460 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.596

GnomAD4 exome AF: 0.566 AC: 604857 AN: 1067758 Hom.: 177353 Cov.: 14 AF XY: 0.571 AC XY: 313017 AN XY: 548132

Gnomad4 AFR exome AF: 0.726

Gnomad4 AMR exome AF: 0.539

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.954

Gnomad4 SAS exome AF: 0.724

Gnomad4 FIN exome AF: 0.591

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.612 AC: 93027 AN: 152080 Hom.: 29481 Cov.: 32 AF XY: 0.620 AC XY: 46073 AN XY: 74356

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.592

Alfa AF: 0.432 Hom.: 1192

Bravo AF: 0.613

Asia WGS AF: 0.764 AC: 2655 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.3
Dann	Benign	0.67

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: rs1293987; hg19: chr1-186265948;