chr16-2110493-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001009944.3(PKD1):c.4674G>A(p.Thr1558Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 1,612,318 control chromosomes in the GnomAD database, including 5,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 411 hom., cov: 34)

Exomes 𝑓: 0.077 ( 4977 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.18

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=-0.71).

BP6

Variant 16-2110493-C-T is Benign according to our data. Variant chr16-2110493-C-T is described in ClinVar as [Benign]. Clinvar id is 256969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2110493-C-T is described in Lovd as [Benign]. Variant chr16-2110493-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-5.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.4674G>A	p.Thr1558Thr	synonymous_variant	Exon 15 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.4674G>A	p.Thr1558Thr	synonymous_variant	Exon 15 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.0637

AC:

9694

AN:

152194

Hom.:

410

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.0509

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.0708

Gnomad FIN

AF:

0.0851

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0808

Gnomad OTH

AF:

0.0722

GnomAD3 exomes

AF:

0.0769

AC:

19137

AN:

248748

Hom.:

874

AF XY:

0.0783

AC XY:

10586

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.00968

Gnomad AMR exome

AF:

0.0492

Gnomad ASJ exome

AF:

0.0968

Gnomad EAS exome

AF:

0.180

Gnomad SAS exome

AF:

0.0737

Gnomad FIN exome

AF:

0.0878

Gnomad NFE exome

AF:

0.0754

Gnomad OTH exome

AF:

0.0725

GnomAD4 exome

AF:

0.0775

AC:

113080

AN:

1460006

Hom.:

4977

Cov.:

AF XY:

0.0781

AC XY:

56758

AN XY:

726292

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.0490

Gnomad4 ASJ exome

AF:

0.0960

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.0747

Gnomad4 FIN exome

AF:

0.0923

Gnomad4 NFE exome

AF:

0.0750

Gnomad4 OTH exome

AF:

0.0741

GnomAD4 genome

AF:

0.0636

AC:

9686

AN:

152312

Hom.:

411

Cov.:

AF XY:

0.0646

AC XY:

4808

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.0508

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.0705

Gnomad4 FIN

AF:

0.0851

Gnomad4 NFE

AF:

0.0808

Gnomad4 OTH

AF:

0.0710

Alfa

AF:

0.0713

Hom.:

190

Bravo

AF:

0.0588

Asia WGS

AF:

0.0920

AC:

319

AN:

3478

EpiCase

AF:

0.0769

EpiControl

AF:

0.0736

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

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

- -

Sep 26, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic kidney disease, adult type

Benign:1

Jun 01, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 c.4674G>A, p.Thr1558Thr variant was identified in7.57% of 9015 control alleles in the Exome Aggregation Consortium (March 14, 2016). According to ACMG guidelines for variant classification based on allele frequency, category BA1, this variant is considered benign and has not been further reviewed (Richards 2015). -

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

-0.71

CADD

Benign

0.10

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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