NM_138694.4:c.11786-30C>T

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.11786-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,575,624 control chromosomes in the GnomAD database, including 24,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1908 hom., cov: 33)

Exomes 𝑓: 0.17 ( 22362 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0380

Publications

5 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:

ENSG00000228689 (HGNC:):

ENSG00000228689 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=-0.82).

BP6

Variant 6-51619550-G-A is Benign according to our data. Variant chr6-51619550-G-A is described in ClinVar as Benign. ClinVar VariationId is 262386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.11786-30C>T		intron_variant	Intron 66 of 66	ENST00000371117.8	NP_619639.3	P08F94-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PKHD1	ENST00000371117.8 link	c.11786-30C>T	intron_variant	Intron 66 of 66	1	NM_138694.4	ENSP00000360158.3	P08F94-1
ENSG00000228689	ENST00000454361.1 link	n.81-2805G>A	intron_variant	Intron 1 of 1	3
ENSG00000228689	ENST00000589278.6 link	n.811-2810G>A	intron_variant	Intron 2 of 2	5
ENSG00000228689	ENST00000650088.1 link	n.222-2805G>A	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22195

AN:

152016

Hom.:

1908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.121

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.135

GnomAD2 exomes

AF:

0.176

AC:

43306

AN:

246564

AF XY:

0.179

show subpopulations

Gnomad AFR exome

AF:

0.0783

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.183

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.173

AC:

245822

AN:

1423490

Hom.:

22362

Cov.:

AF XY:

0.174

AC XY:

123577

AN XY:

710710

show subpopulations

African (AFR)

AF:

0.0715

AC:

2344

AN:

32770

American (AMR)

AF:

0.105

AC:

4682

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

4068

AN:

25876

East Asian (EAS)

AF:

0.324

AC:

12782

AN:

39480

South Asian (SAS)

AF:

0.200

AC:

17067

AN:

85268

European-Finnish (FIN)

AF:

0.178

AC:

9383

AN:

52834

Middle Eastern (MID)

AF:

0.135

AC:

773

AN:

5712

European-Non Finnish (NFE)

AF:

0.172

AC:

184985

AN:

1077902

Other (OTH)

AF:

0.165

AC:

9738

AN:

59008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

9936

19873

29809

39746

49682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6578

13156

19734

26312

32890

<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:

0.146

AC:

22199

AN:

152134

Hom.:

1908

Cov.:

AF XY:

0.149

AC XY:

11073

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0762

AC:

3162

AN:

41514

American (AMR)

AF:

0.117

AC:

1788

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

529

AN:

3464

East Asian (EAS)

AF:

0.358

AC:

1852

AN:

5178

South Asian (SAS)

AF:

0.221

AC:

1065

AN:

4820

European-Finnish (FIN)

AF:

0.182

AC:

1923

AN:

10578

Middle Eastern (MID)

AF:

0.116

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.167

AC:

11371

AN:

67972

Other (OTH)

AF:

0.135

AC:

285

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

950

1900

2851

3801

4751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.157

Hom.:

6874

Bravo

AF:

0.141

Asia WGS

AF:

0.238

AC:

826

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive polycystic kidney disease

Benign:1

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

-0.82

CADD

Benign

1.8

(source)

DANN

Benign

0.26

PhyloP100

0.038

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over