dbSNP rs144933686: PRG4:p.Gln89Gln (chr1-186301659-A-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_005807.6(PRG4):c.267A>G(p.Gln89Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,613,738 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

PRG4
NM_005807.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.92

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

camptodactyly-arthropathy-coxa vara-pericarditis syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Illumina, Labcorp Genetics (formerly Invitae)

PRG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-186301659-A-G is Benign according to our data. Variant chr1-186301659-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2639649.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.93 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005807.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRG4	NM_005807.6	MANE Select	c.267A>G	p.Gln89Gln	synonymous	Exon 4 of 13	NP_005798.3	Q92954-1
PRG4	NM_001127708.3		c.144A>G	p.Gln48Gln	synonymous	Exon 3 of 12	NP_001121180.2	Q92954-2
PRG4	NM_001303232.2		c.267A>G	p.Gln89Gln	synonymous	Exon 4 of 12	NP_001290161.1	Q92954-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRG4	ENST00000445192.7	TSL:5 MANE Select	c.267A>G	p.Gln89Gln	synonymous	Exon 4 of 13	ENSP00000399679.3	Q92954-1
PRG4	ENST00000367483.8	TSL:5	c.144A>G	p.Gln48Gln	synonymous	Exon 3 of 12	ENSP00000356453.4	Q92954-2
PRG4	ENST00000635041.1	TSL:5	c.267A>G	p.Gln89Gln	synonymous	Exon 4 of 12	ENSP00000489292.1	Q92954-6

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000131

AC:

AN:

251472

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000276

AC:

403

AN:

1461634

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

185

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33474

American (AMR)

AF:

0.000112

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000337

AC:

375

AN:

1111790

Other (OTH)

AF:

0.000116

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000178

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00316

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.000181

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.026

(source)

DANN

Benign

0.29

PhyloP100

-4.9

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over