rs9474140

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138694.4(PKHD1):c.527+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,530,006 control chromosomes in the GnomAD database, including 50,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6099 hom., cov: 32)

Exomes 𝑓: 0.25 ( 44860 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.669

Publications

8 publications found

Variant links:

Genes affected

PKHD1 (HGNC:9016): (PKHD1 ciliary IPT domain containing fibrocystin/polyductin) The protein encoded by this gene is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1. [provided by RefSeq, Jul 2008]

PKHD1 Gene-Disease associations (from GenCC):

autosomal recessive polycystic kidney disease
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Orphanet
polycystic kidney disease 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Genomics England PanelApp
Caroli disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PKHD1 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=-0.9).

BP6

Variant 6-52073444-A-G is Benign according to our data. Variant chr6-52073444-A-G is described in ClinVar as Benign. ClinVar VariationId is 96407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.527+19T>C		intron_variant	Intron 7 of 66	ENST00000371117.8	NP_619639.3	P08F94-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8 link	c.527+19T>C		intron_variant	Intron 7 of 66	1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 link	c.527+19T>C		intron_variant	Intron 7 of 60	5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42407

AN:

152034

Hom.:

6092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.267

GnomAD2 exomes

AF:

0.276

AC:

69356

AN:

251244

AF XY:

0.281

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.201

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.433

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.249

AC:

342682

AN:

1377854

Hom.:

44860

Cov.:

AF XY:

0.252

AC XY:

173732

AN XY:

690668

show subpopulations

African (AFR)

AF:

0.313

AC:

9947

AN:

31744

American (AMR)

AF:

0.207

AC:

9218

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

6523

AN:

25590

East Asian (EAS)

AF:

0.426

AC:

16711

AN:

39198

South Asian (SAS)

AF:

0.353

AC:

29782

AN:

84406

European-Finnish (FIN)

AF:

0.298

AC:

15874

AN:

53340

Middle Eastern (MID)

AF:

0.286

AC:

1602

AN:

5598

European-Non Finnish (NFE)

AF:

0.230

AC:

238002

AN:

1035806

Other (OTH)

AF:

0.261

AC:

15023

AN:

57560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

11177

22355

33532

44710

55887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8060

16120

24180

32240

40300

<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:

0.279

AC:

42426

AN:

152152

Hom.:

6099

Cov.:

AF XY:

0.285

AC XY:

21203

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.319

AC:

13228

AN:

41498

American (AMR)

AF:

0.234

AC:

3573

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

886

AN:

3468

East Asian (EAS)

AF:

0.432

AC:

2233

AN:

5172

South Asian (SAS)

AF:

0.371

AC:

1786

AN:

4820

European-Finnish (FIN)

AF:

0.325

AC:

3446

AN:

10606

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.241

AC:

16410

AN:

67990

Other (OTH)

AF:

0.267

AC:

564

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1578

3157

4735

6314

7892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.250

Hom.:

1020

Bravo

AF:

0.272

Asia WGS

AF:

0.391

AC:

1355

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

- -

Oct 09, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive polycystic kidney disease

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 12, 2018

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polycystic kidney disease 4

Benign:1

Jun 19, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.0

(source)

DANN

Benign

0.59

PhyloP100

-0.67

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over