rs2293797

Positions:

• chr14-73258951-C-A

Variant summary

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

The NM_001365906.3(PAPLN):​c.1628-28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,586,834 control chromosomes in the GnomAD database, including 10,914 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 0.12 (1197 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9717 hom.)
• Consequence: PAPLN NM_001365906.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPLN	NM_001365906.3	c.1628-28C>A		intron_variant		ENST00000644200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPLN	ENST00000644200.2	c.1628-28C>A		intron_variant			NM_001365906.3	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17617 AN: 152046 Hom.: 1191 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0901

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.129 AC: 28727 AN: 223062 Hom.: 2598 AF XY: 0.125 AC XY: 15052 AN XY: 120848

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.0508

Gnomad EAS exome AF: 0.0528

Gnomad SAS exome AF: 0.205

Gnomad FIN exome AF: 0.0864

Gnomad NFE exome AF: 0.0905

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.107 AC: 154174 AN: 1434670 Hom.: 9717 Cov.: 31 AF XY: 0.109 AC XY: 77570 AN XY: 712034

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.0505

Gnomad4 EAS exome AF: 0.0634

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.0836

Gnomad4 NFE exome AF: 0.0982

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.116 AC: 17640 AN: 152164 Hom.: 1197 Cov.: 32 AF XY: 0.117 AC XY: 8677 AN XY: 74386

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.0551

Gnomad4 EAS AF: 0.0688

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.0901

Gnomad4 OTH AF: 0.105

Alfa AF: 0.105 Hom.: 582

Bravo AF: 0.125

Asia WGS AF: 0.156 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2293797; hg19: chr14-73725659; COSMIC: COSV104370686; COSMIC: COSV104370686;