chr16-2117873-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001009944.3(PKD1):c.1119C>T(p.Leu373Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 142,122 control chromosomes in the GnomAD database, including 48,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 48164 hom., cov: 30)

Exomes 𝑓: 0.78 ( 295723 hom. )

Failed GnomAD Quality Control

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.08

Publications

12 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 Gene-Disease associations (from GenCC):

autosomal dominant polycystic kidney disease
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
polycystic kidney disease 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
autosomal recessive polycystic kidney disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Caroli disease
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

PKD1 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=-0.86).

BP6

Variant 16-2117873-G-A is Benign according to our data. Variant chr16-2117873-G-A is described in ClinVar as Benign. ClinVar VariationId is 803174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.1119C>T	p.Leu373Leu	synonymous_variant	Exon 5 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.1119C>T	p.Leu373Leu	synonymous_variant	Exon 5 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.829

AC:

117786

AN:

142016

Hom.:

48111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.710

Gnomad AMR

AF:

0.856

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.963

Gnomad SAS

AF:

0.889

Gnomad FIN

AF:

0.814

Gnomad MID

AF:

0.825

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.815

GnomAD2 exomes

AF:

0.895

AC:

84660

AN:

94572

AF XY:

0.894

show subpopulations

Gnomad AFR exome

AF:

0.974

Gnomad AMR exome

AF:

0.930

Gnomad ASJ exome

AF:

0.820

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.847

Gnomad NFE exome

AF:

0.829

Gnomad OTH exome

AF:

0.860

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.778

AC:

788669

AN:

1014150

Hom.:

295723

Cov.:

AF XY:

0.779

AC XY:

399855

AN XY:

513052

show subpopulations

African (AFR)

AF:

0.890

AC:

21374

AN:

24004

American (AMR)

AF:

0.879

AC:

30591

AN:

34792

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

16971

AN:

22440

East Asian (EAS)

AF:

0.914

AC:

30799

AN:

33690

South Asian (SAS)

AF:

0.842

AC:

60604

AN:

71958

European-Finnish (FIN)

AF:

0.799

AC:

27115

AN:

33930

Middle Eastern (MID)

AF:

0.782

AC:

2613

AN:

3342

European-Non Finnish (NFE)

AF:

0.756

AC:

562781

AN:

744750

Other (OTH)

AF:

0.792

AC:

35821

AN:

45244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.566

Heterozygous variant carriers

6785

13571

20356

27142

33927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12176

24352

36528

48704

60880

<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:

0.830

AC:

117892

AN:

142122

Hom.:

48164

Cov.:

AF XY:

0.833

AC XY:

57768

AN XY:

69370

show subpopulations

African (AFR)

AF:

0.906

AC:

34638

AN:

38240

American (AMR)

AF:

0.856

AC:

12327

AN:

14396

Ashkenazi Jewish (ASJ)

AF:

0.767

AC:

2507

AN:

3270

East Asian (EAS)

AF:

0.963

AC:

4667

AN:

4848

South Asian (SAS)

AF:

0.888

AC:

3917

AN:

4410

European-Finnish (FIN)

AF:

0.814

AC:

8214

AN:

10092

Middle Eastern (MID)

AF:

0.818

AC:

229

AN:

280

European-Non Finnish (NFE)

AF:

0.771

AC:

49211

AN:

63808

Other (OTH)

AF:

0.817

AC:

1598

AN:

1956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.576

Heterozygous variant carriers

682

1364

2045

2727

3409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

826

1652

2478

3304

4130

<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:

0.802

Hom.:

4452

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 27, 2025

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Polycystic kidney disease, adult type

Benign:3

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 03, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.85

(source)

DANN

Benign

0.83

PhyloP100

-1.1

PromoterAI

0.033

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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