rs11628713

Positions:

• chr14-73255067-C-T

Variant summary

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

The NM_001365906.3(PAPLN):​c.1627+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,571,484 control chromosomes in the GnomAD database, including 23,507 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 0.16 (2083 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21424 hom.)
• Consequence: PAPLN NM_001365906.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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]

PAPLN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPLN	NM_001365906.3	c.1627+49C>T		intron_variant		ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2	c.1627+49C>T		intron_variant			NM_001365906.3	ENSP00000495882.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24476 AN: 152050 Hom.: 2083 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.160

GnomAD3 exomes AF: 0.163 AC: 30483 AN: 186612 Hom.: 2583 AF XY: 0.170 AC XY: 17033 AN XY: 100456

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.0909

Gnomad ASJ exome AF: 0.177

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.201

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.171 AC: 242920 AN: 1419314 Hom.: 21424 Cov.: 33 AF XY: 0.173 AC XY: 121625 AN XY: 702308

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.0946

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.0876

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.161 AC: 24502 AN: 152170 Hom.: 2083 Cov.: 32 AF XY: 0.161 AC XY: 11956 AN XY: 74390

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0924

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.163

Alfa AF: 0.179 Hom.: 3688

Bravo AF: 0.155

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.45

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: rs11628713; hg19: chr14-73721775; COSMIC: COSV53723544; COSMIC: COSV53723544;