rs116114803

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001009944.3(PKD1):c.10768C>T(p.Leu3590Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,569,998 control chromosomes in the GnomAD database, including 941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 63 hom., cov: 33)

Exomes 𝑓: 0.032 ( 878 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.335

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 (HGNC:):

PKD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 16-2093864-G-A is Benign according to our data. Variant chr16-2093864-G-A is described in ClinVar as [Benign]. Clinvar id is 256894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2093864-G-A is described in Lovd as [Benign]. Variant chr16-2093864-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.335 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0231 (3514/152294) while in subpopulation NFE AF= 0.0379 (2577/68000). AF 95% confidence interval is 0.0367. There are 63 homozygotes in gnomad4. There are 1656 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3514 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1	NM_001009944.3 linkuse as main transcript	c.10768C>T	p.Leu3590Leu	synonymous_variant	36/46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 linkuse as main transcript	c.10768C>T	p.Leu3590Leu	synonymous_variant	36/46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3512

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00632

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.0296

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0379

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0220

AC:

4115

AN:

187406

Hom.:

AF XY:

0.0223

AC XY:

2276

AN XY:

102174

show subpopulations

Gnomad AFR exome

AF:

0.00659

Gnomad AMR exome

AF:

0.00782

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.0371

Gnomad NFE exome

AF:

0.0350

Gnomad OTH exome

AF:

0.0233

GnomAD4 exome

AF:

0.0324

AC:

45921

AN:

1417704

Hom.:

878

Cov.:

AF XY:

0.0319

AC XY:

22428

AN XY:

703030

show subpopulations

Gnomad4 AFR exome

AF:

0.00498

Gnomad4 AMR exome

AF:

0.00834

Gnomad4 ASJ exome

AF:

0.0166

Gnomad4 EAS exome

AF:

0.0000532

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.0348

Gnomad4 NFE exome

AF:

0.0376

Gnomad4 OTH exome

AF:

0.0258

GnomAD4 genome

AF:

0.0231

AC:

3514

AN:

152294

Hom.:

Cov.:

AF XY:

0.0222

AC XY:

1656

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00630

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.0296

Gnomad4 NFE

AF:

0.0379

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0241

Hom.:

Bravo

AF:

0.0210

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Polycystic kidney disease, adult type

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 15, 2017	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 08, 2020	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 27, 2020	This variant is associated with the following publications: (PMID: 19686598, 11058904, 15772804) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant polycystic kidney disease

Benign:1

Benign, criteria provided, single submitter

research

Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.8

DANN

Benign

0.72

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over