rs9928278

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001009944.3(PKD1):c.8949-17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,610,012 control chromosomes in the GnomAD database, including 29,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6793 hom., cov: 33)

Exomes 𝑓: 0.16 ( 22992 hom. )

Consequence

PKD1
NM_001009944.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.41

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-2102650-T-C is Benign according to our data. Variant chr16-2102650-T-C is described in ClinVar as [Benign]. Clinvar id is 257034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2102650-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.8949-17A>G		intron_variant	Intron 24 of 45	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.8949-17A>G		intron_variant	Intron 24 of 45	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38407

AN:

152008

Hom.:

6771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0714

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.241

GnomAD3 exomes

AF:

0.160

AC:

39456

AN:

246746

Hom.:

4651

AF XY:

0.154

AC XY:

20697

AN XY:

134674

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.000274

Gnomad SAS exome

AF:

0.0728

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.164

AC:

239165

AN:

1457886

Hom.:

22992

Cov.:

AF XY:

0.161

AC XY:

116601

AN XY:

725288

show subpopulations

Gnomad4 AFR exome

AF:

0.513

Gnomad4 AMR exome

AF:

0.121

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.0752

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.253

AC:

38474

AN:

152126

Hom.:

6793

Cov.:

AF XY:

0.247

AC XY:

18391

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.499

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0708

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.163

Gnomad4 OTH

AF:

0.239

Alfa

AF:

0.217

Hom.:

1234

Bravo

AF:

0.264

Asia WGS

AF:

0.0730

AC:

255

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

Feb 01, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic kidney disease, adult type

Benign:1

Jul 07, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

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

1.7

DANN

Benign

0.37

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

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