chr16-2090971-G-A

Variant names:

Variant summary

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

The NM_001009944.3(PKD1):c.11916C>T(p.Arg3972Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0298 in 1,543,072 control chromosomes in the GnomAD database, including 825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R3972R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.022 ( 58 hom., cov: 34)

Exomes 𝑓: 0.031 ( 767 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.650

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-2090971-G-A is Benign according to our data. Variant chr16-2090971-G-A is described in ClinVar as [Benign]. Clinvar id is 256909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2090971-G-A is described in Lovd as [Benign]. Variant chr16-2090971-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.65 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0216 (3291/152196) while in subpopulation NFE AF= 0.0355 (2410/67972). AF 95% confidence interval is 0.0343. There are 58 homozygotes in gnomad4. There are 1549 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3291 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.11916C>T	p.Arg3972Arg	synonymous_variant	Exon 43 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.11916C>T	p.Arg3972Arg	synonymous_variant	Exon 43 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3289

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00584

Gnomad AMI

AF:

0.0473

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00765

Gnomad FIN

AF:

0.0314

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0355

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0203

AC:

2806

AN:

138110

Hom.:

AF XY:

0.0208

AC XY:

1580

AN XY:

76056

show subpopulations

Gnomad AFR exome

AF:

0.00553

Gnomad AMR exome

AF:

0.00722

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.0426

Gnomad NFE exome

AF:

0.0350

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0307

AC:

42693

AN:

1390876

Hom.:

767

Cov.:

AF XY:

0.0302

AC XY:

20774

AN XY:

687362

show subpopulations

Gnomad4 AFR exome

AF:

0.00447

Gnomad4 AMR exome

AF:

0.00748

Gnomad4 ASJ exome

AF:

0.0149

Gnomad4 EAS exome

AF:

0.0000828

Gnomad4 SAS exome

AF:

0.0113

Gnomad4 FIN exome

AF:

0.0392

Gnomad4 NFE exome

AF:

0.0353

Gnomad4 OTH exome

AF:

0.0242

GnomAD4 genome

AF:

0.0216

AC:

3291

AN:

152196

Hom.:

Cov.:

AF XY:

0.0208

AC XY:

1549

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00583

Gnomad4 AMR

AF:

0.00863

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.0314

Gnomad4 NFE

AF:

0.0355

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0149

Hom.:

Bravo

AF:

0.0193

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Polycystic kidney disease, adult type

Benign:2

May 30, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 08, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Dec 03, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 10987650, 15772804) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autosomal dominant polycystic kidney disease

Benign:1

Jan 01, 2019

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.6

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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