rs8017937

chr14-73252595-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365906.3(PAPLN):c.968-54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,587,068 control chromosomes in the GnomAD database, including 13,838 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 0.17 (3393 hom., cov: 33)
  • Exomes 𝑓: 0.10 (10445 hom.)
• Consequence: PAPLN NM_001365906.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

Genes affected

PAPLN (HGNC:19262): (papilin, proteoglycan like sulfated glycoprotein) Predicted to enable metalloendopeptidase activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in basement membrane. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPLN	NM_001365906.3	c.968-54G>A		intron_variant		ENST00000644200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPLN	ENST00000644200.2	c.968-54G>A		intron_variant			NM_001365906.3	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25864 AN: 152078 Hom.: 3382 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.0673

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.105 AC: 150240 AN: 1434872 Hom.: 10445 AF XY: 0.107 AC XY: 75925 AN XY: 711444

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.0834

Gnomad4 EAS exome AF: 0.0730

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.0682

Gnomad4 NFE exome AF: 0.0865

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.170 AC: 25922 AN: 152196 Hom.: 3393 Cov.: 33 AF XY: 0.168 AC XY: 12538 AN XY: 74418

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.0876

Gnomad4 EAS AF: 0.0679

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.0673

Gnomad4 NFE AF: 0.0813

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0974 Hom.: 917

Bravo AF: 0.184

Asia WGS AF: 0.174 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.32
Dann	Benign	0.66

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: rs8017937; hg19: chr14-73719303; COSMIC: COSV53717479; COSMIC: COSV53717479;