rs9928278

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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:6

Conservation

PhyloP100: -1.41

Publications

10 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: Orphanet, ClinGen
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 -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 VariationId is 257034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	NM_001009944.3	MANE Select	c.8949-17A>G		intron	N/A	NP_001009944.3	P98161-1
	PKD1	NM_000296.4		c.8949-17A>G		intron	N/A	NP_000287.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PKD1	ENST00000262304.9	TSL:1 MANE Select	c.8949-17A>G	intron	N/A	ENSP00000262304.4	P98161-1
PKD1	ENST00000423118.5	TSL:1	c.8949-17A>G	intron	N/A	ENSP00000399501.1	P98161-3
PKD1	ENST00000480227.5	TSL:1	n.686-17A>G	intron	N/A

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

GnomAD2 exomes

AF:

0.160

AC:

39456

AN:

246746

AF XY:

0.154

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 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

African (AFR)

AF:

0.513

AC:

17129

AN:

33368

American (AMR)

AF:

0.121

AC:

5419

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

6157

AN:

26116

East Asian (EAS)

AF:

0.000403

AC:

AN:

39698

South Asian (SAS)

AF:

0.0752

AC:

6480

AN:

86168

European-Finnish (FIN)

AF:

0.182

AC:

9448

AN:

52024

Middle Eastern (MID)

AF:

0.231

AC:

1002

AN:

4344

European-Non Finnish (NFE)

AF:

0.165

AC:

182880

AN:

1111296

Other (OTH)

AF:

0.177

AC:

10634

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

11910

23819

35729

47638

59548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6586

13172

19758

26344

32930

<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:

0.253

AC:

38474

AN:

152126

Hom.:

6793

Cov.:

AF XY:

0.247

AC XY:

18391

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.499

AC:

20705

AN:

41484

American (AMR)

AF:

0.186

AC:

2840

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

804

AN:

3468

East Asian (EAS)

AF:

0.00174

AC:

AN:

5172

South Asian (SAS)

AF:

0.0708

AC:

342

AN:

4828

European-Finnish (FIN)

AF:

0.190

AC:

2017

AN:

10590

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11089

AN:

67970

Other (OTH)

AF:

0.239

AC:

505

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1374

2748

4123

5497

6871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.206

Hom.:

1868

Bravo

AF:

0.264

Asia WGS

AF:

0.0730

AC:

255

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Autosomal dominant polycystic kidney disease (1)

not provided (1)

Polycystic kidney disease, adult type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.7

(source)

DANN

Benign

0.37

PhyloP100

-1.4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over