rs9382044

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.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

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=-0.87).

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 rank	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.7733+33C>T		intron_variant	Intron 48 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.7733+33C>T		intron_variant	Intron 48 of 66	1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 link	c.7733+33C>T		intron_variant	Intron 48 of 60	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

GnomAD2 exomes

AF:

0.446

AC:

110795

AN:

248648

AF XY:

0.436

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 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

African (AFR)

AF:

0.419

AC:

13870

AN:

33106

American (AMR)

AF:

0.634

AC:

28242

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

6526

AN:

25996

East Asian (EAS)

AF:

0.828

AC:

32755

AN:

39576

South Asian (SAS)

AF:

0.514

AC:

44084

AN:

85742

European-Finnish (FIN)

AF:

0.436

AC:

23124

AN:

53070

Middle Eastern (MID)

AF:

0.268

AC:

1541

AN:

5748

European-Non Finnish (NFE)

AF:

0.310

AC:

340725

AN:

1098204

Other (OTH)

AF:

0.363

AC:

21745

AN:

59844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

14950

29900

44849

59799

74749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.403

AC:

61210

AN:

152016

Hom.:

13527

Cov.:

AF XY:

0.418

AC XY:

31048

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.432

AC:

17912

AN:

41474

American (AMR)

AF:

0.532

AC:

8107

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

901

AN:

3466

East Asian (EAS)

AF:

0.852

AC:

4408

AN:

5176

South Asian (SAS)

AF:

0.539

AC:

2599

AN:

4826

European-Finnish (FIN)

AF:

0.453

AC:

4785

AN:

10566

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.317

AC:

21534

AN:

67942

Other (OTH)

AF:

0.366

AC:

774

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1764

3529

5293

7058

8822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.344

Hom.:

2029

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

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 19, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.5

(source)

DANN

Benign

0.77

PhyloP100

-0.0060

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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rs9382044

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