rs754015180

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The ENST00000262304.9(PKD1):c.11713-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,420,784 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

PKD1
ENST00000262304.9 splice_region, intron

Scores

Splicing: ADA: 0.04043

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.13

Publications

2 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: ClinGen, Orphanet
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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 16-2091177-G-A is Benign according to our data. Variant chr16-2091177-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 811770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000113 (144/1271422) while in subpopulation EAS AF = 0.00479 (132/27564). AF 95% confidence interval is 0.00412. There are 1 homozygotes in GnomAdExome4. There are 76 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262304.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	NM_001009944.3	MANE Select	c.11713-3C>T		splice_region intron	N/A	NP_001009944.3
	PKD1	NM_000296.4		c.11710-3C>T		splice_region intron	N/A	NP_000287.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PKD1	ENST00000262304.9	TSL:1 MANE Select	c.11713-3C>T	splice_region intron	N/A	ENSP00000262304.4
PKD1	ENST00000423118.5	TSL:1	c.11710-3C>T	splice_region intron	N/A	ENSP00000399501.1
PKD1	ENST00000487932.5	TSL:5	n.*2906-3C>T	splice_region intron	N/A	ENSP00000457132.1

Frequencies

GnomAD3 genomes

AF:

0.0000335

AC:

AN:

149254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000792

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000124

AC:

AN:

64304

AF XY:

0.000134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00159

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000317

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000113

AC:

144

AN:

1271422

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

625772

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24718

American (AMR)

AF:

0.00

AC:

AN:

18910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18918

East Asian (EAS)

AF:

0.00479

AC:

132

AN:

27564

South Asian (SAS)

AF:

0.00

AC:

AN:

64996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3592

European-Non Finnish (NFE)

AF:

0.00000874

AC:

AN:

1029380

Other (OTH)

AF:

0.0000582

AC:

AN:

51532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000335

AC:

AN:

149362

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72756

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41106

American (AMR)

AF:

0.00

AC:

AN:

14814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.000794

AC:

AN:

5038

South Asian (SAS)

AF:

0.00

AC:

AN:

4746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67108

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Polycystic kidney disease, adult type (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.040

dbscSNV1_RF

Benign

0.24

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over