NM_001009944.3:c.8161+12C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001009944.3(PKD1):c.8161+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000379 in 1,507,316 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 20)

Exomes 𝑓: 0.00030 ( 5 hom. )

Consequence

PKD1
NM_001009944.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.673

Publications

0 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=-0.93).

BP6

Variant 16-2104486-G-A is Benign according to our data. Variant chr16-2104486-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00112 (166/148232) while in subpopulation AFR AF = 0.00335 (131/39160). AF 95% confidence interval is 0.00288. There are 2 homozygotes in GnomAd4. There are 82 alleles in the male GnomAd4 subpopulation. Median coverage is 20. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

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.8161+12C>T		intron	N/A	NP_001009944.3	P98161-1
	PKD1	NM_000296.4		c.8161+12C>T		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.8161+12C>T	intron	N/A	ENSP00000262304.4	P98161-1
PKD1	ENST00000423118.5	TSL:1	c.8161+12C>T	intron	N/A	ENSP00000399501.1	P98161-3
PKD1	ENST00000567946.1	TSL:5	c.220+12C>T	intron	N/A	ENSP00000457984.1	H3BV77

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

159

AN:

148118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000666

Gnomad ASJ

AF:

0.00290

Gnomad EAS

AF:

0.000812

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000119

Gnomad OTH

AF:

0.00146

GnomAD2 exomes

AF:

0.000441

AC:

AN:

151966

AF XY:

0.000412

show subpopulations

Gnomad AFR exome

AF:

0.00426

Gnomad AMR exome

AF:

0.0000788

Gnomad ASJ exome

AF:

0.00156

Gnomad EAS exome

AF:

0.0000828

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000686

GnomAD4 exome

AF:

0.000298

AC:

405

AN:

1359084

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

199

AN XY:

673434

show subpopulations

African (AFR)

AF:

0.00458

AC:

137

AN:

29942

American (AMR)

AF:

0.000191

AC:

AN:

36614

Ashkenazi Jewish (ASJ)

AF:

0.00229

AC:

AN:

24882

East Asian (EAS)

AF:

0.000136

AC:

AN:

36718

South Asian (SAS)

AF:

0.000214

AC:

AN:

79304

European-Finnish (FIN)

AF:

0.0000237

AC:

AN:

42114

Middle Eastern (MID)

AF:

0.000746

AC:

AN:

4024

European-Non Finnish (NFE)

AF:

0.000136

AC:

143

AN:

1048872

Other (OTH)

AF:

0.000618

AC:

AN:

56614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.00112

AC:

166

AN:

148232

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

72342

show subpopulations

African (AFR)

AF:

0.00335

AC:

131

AN:

39160

American (AMR)

AF:

0.000665

AC:

AN:

15040

Ashkenazi Jewish (ASJ)

AF:

0.00290

AC:

AN:

3444

East Asian (EAS)

AF:

0.000814

AC:

AN:

4914

South Asian (SAS)

AF:

0.00

AC:

AN:

4670

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000119

AC:

AN:

67244

Other (OTH)

AF:

0.00145

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000779

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Polycystic kidney disease, adult type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.33

(source)

DANN

Benign

0.83

PhyloP100

-0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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