Variant rs9382044 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138694.4(PKHD1):c.7733+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,597,854 control chromosomes in the GnomAD database, including 114,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13527 hom., cov: 33)

Exomes 𝑓: 0.35 ( 101390 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.00600

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:

PKHD1 (HGNC:):

PKHD1 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=-0.87).

BP6

Variant 6-51867830-G-A is Benign according to our data. Variant chr6-51867830-G-A is described in ClinVar as [Benign]. Clinvar id is 262412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKHD1	NM_138694.4 linkuse as main transcript	c.7733+33C>T		intron_variant		ENST00000371117.8	NP_619639.3	P08F94-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8 linkuse as main transcript	c.7733+33C>T		intron_variant		1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 linkuse as main transcript	c.7733+33C>T		intron_variant		5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61171

AN:

151898

Hom.:

13518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.432

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.368

GnomAD3 exomes

AF:

0.446

AC:

110795

AN:

248648

Hom.:

28719

AF XY:

0.436

AC XY:

58731

AN XY:

134718

show subpopulations

Gnomad AFR exome

AF:

0.435

Gnomad AMR exome

AF:

0.654

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.868

Gnomad SAS exome

AF:

0.517

Gnomad FIN exome

AF:

0.450

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.372

GnomAD4 exome

AF:

0.355

AC:

512612

AN:

1445838

Hom.:

101390

Cov.:

AF XY:

0.358

AC XY:

257772

AN XY:

720194

show subpopulations

Gnomad4 AFR exome

AF:

0.419

Gnomad4 AMR exome

AF:

0.634

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.828

Gnomad4 SAS exome

AF:

0.514

Gnomad4 FIN exome

AF:

0.436

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.363

GnomAD4 genome

AF:

0.403

AC:

61210

AN:

152016

Hom.:

13527

Cov.:

AF XY:

0.418

AC XY:

31048

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.432

Gnomad4 AMR

AF:

0.532

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.852

Gnomad4 SAS

AF:

0.539

Gnomad4 FIN

AF:

0.453

Gnomad4 NFE

AF:

0.317

Gnomad4 OTH

AF:

0.366

Alfa

AF:

0.342

Hom.:

1956

Bravo

AF:

0.407

Asia WGS

AF:

0.622

AC:

2163

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Polycystic kidney disease 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.5

DANN

Benign

0.77

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