14-73257387-A-G

Position:

• chr14-73257387-A-G

Variant summary

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

The NM_001365906.3(PAPLN):​c.1628-1592A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 149,032 control chromosomes in the GnomAD database, including 26,130 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 0.59 (26130 hom., cov: 31)
• Consequence: PAPLN NM_001365906.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPLN	NM_001365906.3	c.1628-1592A>G		intron_variant		ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2	c.1628-1592A>G		intron_variant			NM_001365906.3	ENSP00000495882.2

Frequencies

GnomAD3 genomes AF: 0.592 AC: 88144 AN: 148916 Hom.: 26088 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.592 AC: 88244 AN: 149032 Hom.: 26130 Cov.: 31 AF XY: 0.597 AC XY: 43387 AN XY: 72676

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.576

Alfa AF: 0.561 Hom.: 2965

Bravo AF: 0.595

Asia WGS AF: 0.665 AC: 2311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.73
DANN	Benign	0.62

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: rs6574115; hg19: chr14-73724095;