Variant 1-186296816-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.423

Variant links:

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]

PRG4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
PRG4	NM_005807.6 linkuse as main transcript	c.-30-30T>A		intron_variant		ENST00000445192.7	NP_005798.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRG4	ENST00000445192.7 linkuse as main transcript	c.-30-30T>A		intron_variant		5	NM_005807.6	ENSP00000399679	P2	Q92954-1

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

92966

AN:

151962

Hom.:

29460

Cov.:

show subpopulations

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.:

AF XY:

0.571

AC XY:

313017

AN XY:

548132

show subpopulations

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.:

AF XY:

0.620

AC XY:

46073

AN XY:

74356

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over