dbSNP rs8017937: PAPLN:c.968-54G>A (chr14-73252595-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001365906.3(PAPLN):c.968-54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,587,068 control chromosomes in the GnomAD database, including 13,838 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 0.17 ( 3393 hom., cov: 33)

Exomes 𝑓: 0.10 ( 10445 hom. )

Consequence

PAPLN
NM_001365906.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00100

Publications

6 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365906.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PAPLN	NM_001365906.3	MANE Select	c.968-54G>A	intron	N/A	NP_001352835.1
PAPLN	NM_001365907.2		c.968-54G>A	intron	N/A	NP_001352836.1
PAPLN	NM_173462.4		c.887-54G>A	intron	N/A	NP_775733.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PAPLN	ENST00000644200.2	MANE Select	c.968-54G>A	intron	N/A	ENSP00000495882.2
PAPLN	ENST00000216658.9	TSL:1	n.968-54G>A	intron	N/A	ENSP00000216658.5
PAPLN	ENST00000555123.5	TSL:1	n.887-54G>A	intron	N/A	ENSP00000452455.1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25864

AN:

152078

Hom.:

3382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.0876

Gnomad EAS

AF:

0.0675

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.0673

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0813

Gnomad OTH

AF:

0.139

GnomAD4 exome

AF:

0.105

AC:

150240

AN:

1434872

Hom.:

10445

AF XY:

0.107

AC XY:

75925

AN XY:

711444

show subpopulations

African (AFR)

AF:

0.368

AC:

12208

AN:

33162

American (AMR)

AF:

0.201

AC:

8696

AN:

43326

Ashkenazi Jewish (ASJ)

AF:

0.0834

AC:

2082

AN:

24968

East Asian (EAS)

AF:

0.0730

AC:

2868

AN:

39272

South Asian (SAS)

AF:

0.227

AC:

18994

AN:

83544

European-Finnish (FIN)

AF:

0.0682

AC:

3081

AN:

45172

Middle Eastern (MID)

AF:

0.0729

AC:

409

AN:

5614

European-Non Finnish (NFE)

AF:

0.0865

AC:

95239

AN:

1100394

Other (OTH)

AF:

0.112

AC:

6663

AN:

59420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

6905

13810

20714

27619

34524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3948

7896

11844

15792

19740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.170

AC:

25922

AN:

152196

Hom.:

3393

Cov.:

AF XY:

0.168

AC XY:

12538

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.359

AC:

14907

AN:

41474

American (AMR)

AF:

0.171

AC:

2619

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0876

AC:

304

AN:

3472

East Asian (EAS)

AF:

0.0679

AC:

351

AN:

5170

South Asian (SAS)

AF:

0.232

AC:

1120

AN:

4826

European-Finnish (FIN)

AF:

0.0673

AC:

715

AN:

10618

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0813

AC:

5529

AN:

68018

Other (OTH)

AF:

0.138

AC:

292

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1005

2010

3015

4020

5025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.111

Hom.:

1640

Bravo

AF:

0.184

Asia WGS

AF:

0.174

AC:

607

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.32

(source)

DANN

Benign

0.66

PhyloP100

-0.0010

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over