NM_005807.6:c.76+1017C>A

Variant names:

• chr1-186297968-C-A
• rs1293989
• NM_005807.6:c.76+1017C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005807.6(PRG4):​c.76+1017C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,146 control chromosomes in the GnomAD database, including 30,451 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (30451 hom., cov: 33)
• Consequence: PRG4 NM_005807.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 4 publications found

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: Labcorp Genetics (formerly Invitae), Illumina, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRG4	NM_005807.6	c.76+1017C>A		intron_variant	Intron 2 of 12	ENST00000445192.7	NP_005798.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRG4	ENST00000445192.7	c.76+1017C>A		intron_variant	Intron 2 of 12	5	NM_005807.6	ENSP00000399679.3

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94318 AN: 152030 Hom.: 30425 Cov.: 33

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.601

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.620 AC: 94386 AN: 152146 Hom.: 30451 Cov.: 33 AF XY: 0.628 AC XY: 46718 AN XY: 74380

African (AFR) AF: 0.757 AC: 31423 AN: 41506

American (AMR) AF: 0.556 AC: 8499 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1862 AN: 3470

East Asian (EAS) AF: 0.940 AC: 4861 AN: 5174

South Asian (SAS) AF: 0.744 AC: 3588 AN: 4824

European-Finnish (FIN) AF: 0.595 AC: 6300 AN: 10582

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.528 AC: 35872 AN: 67988

Other (OTH) AF: 0.597 AC: 1261 AN: 2112

Alfa AF: 0.553 Hom.: 70304

Bravo AF: 0.623

Asia WGS AF: 0.768 AC: 2669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.089
DANN	Benign	0.48
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1293989; hg19: chr1-186267100;