rs9395699

Positions:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
PKHD1	NM_138694.4 linkuse as main transcript	c.11786-30C>T		intron_variant		ENST00000371117.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
PKHD1	ENST00000371117.8 linkuse as main transcript	c.11786-30C>T	intron_variant	1	NM_138694.4	P2	P08F94-1
	ENST00000589278.6 linkuse as main transcript	n.811-2810G>A	intron_variant, non_coding_transcript_variant	5
	ENST00000454361.1 linkuse as main transcript	n.81-2805G>A	intron_variant, non_coding_transcript_variant	3
	ENST00000650088.1 linkuse as main transcript	n.222-2805G>A	intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes

AF:

0.176

AC:

43306

AN:

246564

Hom.:

4459

AF XY:

0.179

AC XY:

24004

AN XY:

133922

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 SAS exome

AF:

0.203

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

Gnomad4 AFR exome

AF:

0.0715

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.324

Gnomad4 SAS exome

AF:

0.200

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.146

AC:

22199

AN:

152134

Hom.:

1908

Cov.:

AF XY:

0.149

AC XY:

11073

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0762

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.358

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.157

Hom.:

3244

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive polycystic kidney disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 12, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Polycystic kidney disease 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

DANN

Benign

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over