rs567482892

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001009944.3(PKD1):c.11682C>T(p.Ser3894Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,236,480 control chromosomes in the GnomAD database, including 308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 23 hom., cov: 33)

Exomes 𝑓: 0.021 ( 285 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.86

Publications

4 publications found

Variant links:

Genes affected

PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]

PKD1 links:

PKD1-AS1 (HGNC:56035): (PKD1 antisense RNA 1)

PKD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 16-2091453-G-A is Benign according to our data. Variant chr16-2091453-G-A is described in ClinVar as Benign. ClinVar VariationId is 256908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.86 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0119 (1768/148828) while in subpopulation NFE AF = 0.0194 (1293/66760). AF 95% confidence interval is 0.0185. There are 23 homozygotes in GnomAd4. There are 841 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.11682C>T	p.Ser3894Ser	synonymous_variant	Exon 42 of 46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.11682C>T	p.Ser3894Ser	synonymous_variant	Exon 42 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1768

AN:

148720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00344

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.00797

Gnomad ASJ

AF:

0.00205

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0194

Gnomad OTH

AF:

0.0107

GnomAD2 exomes

AF:

0.0179

AC:

126

AN:

7026

AF XY:

0.0156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0286

Gnomad ASJ exome

AF:

0.00213

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0342

Gnomad NFE exome

AF:

0.0267

Gnomad OTH exome

AF:

0.00943

GnomAD4 exome

AF:

0.0206

AC:

22388

AN:

1087652

Hom.:

285

Cov.:

AF XY:

0.0203

AC XY:

10666

AN XY:

524320

show subpopulations

African (AFR)

AF:

0.00263

AC:

AN:

19750

American (AMR)

AF:

0.0110

AC:

AN:

6560

Ashkenazi Jewish (ASJ)

AF:

0.00326

AC:

AN:

11974

East Asian (EAS)

AF:

0.0000534

AC:

AN:

18712

South Asian (SAS)

AF:

0.00138

AC:

AN:

41338

European-Finnish (FIN)

AF:

0.0185

AC:

445

AN:

24078

Middle Eastern (MID)

AF:

0.00320

AC:

AN:

2814

European-Non Finnish (NFE)

AF:

0.0227

AC:

20897

AN:

920796

Other (OTH)

AF:

0.0196

AC:

816

AN:

41630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1105

2210

3316

4421

5526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

924

1848

2772

3696

4620

<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:

0.0119

AC:

1768

AN:

148828

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

841

AN XY:

72568

show subpopulations

African (AFR)

AF:

0.00343

AC:

141

AN:

41160

American (AMR)

AF:

0.00796

AC:

119

AN:

14948

Ashkenazi Jewish (ASJ)

AF:

0.00205

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

5100

South Asian (SAS)

AF:

0.00271

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.0169

AC:

158

AN:

9368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0194

AC:

1293

AN:

66760

Other (OTH)

AF:

0.0106

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

100

201

301

402

502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0161

Hom.:

Bravo

AF:

0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 25, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polycystic kidney disease, adult type

Benign:2

Sep 25, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 30, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 22, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 15772804, 17574468, 18837007, 22008521, 22383692, 24374109) -

Polycystic kidney disease

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

The PKD1 p.Ser3894Ser variant was identified in 11 of 1112 proband chromosomes (frequency: 0.01) from individuals or families with ADPKD (Bataille 2011, Garcia-Gonzalez 2007, Rossetti 2012, Peltola 2005). The variant was also identified in dbSNP (ID: rs567482892) as â€šÃ„ÃºN/Aâ€šÃ„Ã¹ and the ADPKD Mutation Database (as likely neutral). This variant was identified in the 1000 Genomes Project in 21 of 5000 chromosomes (frequency: 0.004), the Exome Aggregation Consortium database (August 8, 2016) in 8 (1 homozygous) of 462 chromosomes (freq. 0.02) in the following populations: European in 5 of 40 chromosomes (freq. 0.13), Finnish in 1 of 2 chromosomes (freq. 0.5), Latino in 1 of 10 chromosomes (freq. 0.1), South Asian in 1 of 398 chromosomes (freq. 0.003), although this low number of observations and low frequency is not substantive enough to determine the prevalence of the variant in the general population and its relationship to disease. The p.Ser3894Ser variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In addition, the variant classified as a polymorphism by number of population and research studies (Bataille 2011, Garcia-Gonzalez 2007, Rossetti 2012, Peltola 2005). In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.9

(source)

DANN

Benign

0.91

PhyloP100

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism

(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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over