dbSNP rs2293797: PAPLN:c.1628-28C>A (chr14-73258951-C-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.1628-28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,586,834 control chromosomes in the GnomAD database, including 10,914 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 0.12 ( 1197 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9717 hom. )

Consequence

PAPLN
NM_001365906.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.447

Publications

8 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

new If you want to explore the variant's impact on the transcript NM_001365906.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 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	UniProt
PAPLN	NM_001365906.3	MANE Select	c.1628-28C>A	intron	N/A	NP_001352835.1	O95428-1
PAPLN	NM_001365907.2		c.1628-28C>A	intron	N/A	NP_001352836.1	O95428-5
PAPLN	NM_173462.4		c.1547-28C>A	intron	N/A	NP_775733.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PAPLN	ENST00000644200.2	MANE Select	c.1628-28C>A	intron	N/A	ENSP00000495882.2	O95428-1
PAPLN	ENST00000216658.9	TSL:1	n.1628-28C>A	intron	N/A	ENSP00000216658.5	B5MDP7
PAPLN	ENST00000555123.5	TSL:1	n.1547-28C>A	intron	N/A	ENSP00000452455.1	G3V5P6

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17617

AN:

152046

Hom.:

1191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.0551

Gnomad EAS

AF:

0.0689

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.0814

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0901

Gnomad OTH

AF:

0.105

GnomAD2 exomes

AF:

0.129

AC:

28727

AN:

223062

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.0508

Gnomad EAS exome

AF:

0.0528

Gnomad FIN exome

AF:

0.0864

Gnomad NFE exome

AF:

0.0905

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.107

AC:

154174

AN:

1434670

Hom.:

9717

Cov.:

AF XY:

0.109

AC XY:

77570

AN XY:

712034

show subpopulations

African (AFR)

AF:

0.144

AC:

4709

AN:

32798

American (AMR)

AF:

0.265

AC:

10989

AN:

41422

Ashkenazi Jewish (ASJ)

AF:

0.0505

AC:

1244

AN:

24646

East Asian (EAS)

AF:

0.0634

AC:

2458

AN:

38774

South Asian (SAS)

AF:

0.197

AC:

16199

AN:

82100

European-Finnish (FIN)

AF:

0.0836

AC:

4338

AN:

51920

Middle Eastern (MID)

AF:

0.0591

AC:

335

AN:

5672

European-Non Finnish (NFE)

AF:

0.0982

AC:

107780

AN:

1098042

Other (OTH)

AF:

0.103

AC:

6122

AN:

59296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6876

13751

20627

27502

34378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4280

8560

12840

17120

21400

<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:

0.116

AC:

17640

AN:

152164

Hom.:

1197

Cov.:

AF XY:

0.117

AC XY:

8677

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.148

AC:

6147

AN:

41494

American (AMR)

AF:

0.173

AC:

2638

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0551

AC:

191

AN:

3468

East Asian (EAS)

AF:

0.0688

AC:

356

AN:

5172

South Asian (SAS)

AF:

0.204

AC:

983

AN:

4818

European-Finnish (FIN)

AF:

0.0814

AC:

863

AN:

10600

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0901

AC:

6130

AN:

68012

Other (OTH)

AF:

0.105

AC:

221

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

762

1524

2287

3049

3811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.0994

Hom.:

1582

Bravo

AF:

0.125

Asia WGS

AF:

0.156

AC:

546

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.1

(source)

DANN

Benign

0.29

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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