chr14-73257387-A-G

Variant names:

• chr14-73257387-A-G
• rs6574115
• NM_001365906.3:c.1628-1592A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PAPLN	NM_001365906.3	c.1628-1592A>G		intron_variant	Intron 14 of 26	ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2	c.1628-1592A>G		intron_variant	Intron 14 of 26		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

African (AFR) AF: 0.683 AC: 27773 AN: 40652

American (AMR) AF: 0.671 AC: 9953 AN: 14838

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1709 AN: 3408

East Asian (EAS) AF: 0.735 AC: 3776 AN: 5136

South Asian (SAS) AF: 0.664 AC: 3113 AN: 4688

European-Finnish (FIN) AF: 0.531 AC: 5344 AN: 10060

Middle Eastern (MID) AF: 0.455 AC: 132 AN: 290

European-Non Finnish (NFE) AF: 0.521 AC: 34917 AN: 67014

Other (OTH) AF: 0.576 AC: 1181 AN: 2052

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6574115; hg19: chr14-73724095;