rs1047849

Positions:

• chr14-73274478-T-C

Variant summary

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

The NM_001365906.3(PAPLN):​c.*1814T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,208 control chromosomes in the GnomAD database, including 2,738 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 (2738 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PAPLN NM_001365906.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPLN	NM_001365906.3	c.*1814T>C		3_prime_UTR_variant	27/27	ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2	c.*1814T>C		3_prime_UTR_variant	27/27		NM_001365906.3	ENSP00000495882.2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23995 AN: 152088 Hom.: 2738 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0466

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.158 AC: 23991 AN: 152206 Hom.: 2738 Cov.: 32 AF XY: 0.156 AC XY: 11639 AN XY: 74408

Gnomad4 AFR AF: 0.0404

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.144

Alfa AF: 0.204 Hom.: 4522

Bravo AF: 0.142

Asia WGS AF: 0.0340 AC: 120 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	2.4
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1047849; hg19: chr14-73741186;