NM_138694.4:c.2407+50C>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.2407+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,569,940 control chromosomes in the GnomAD database, including 196,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14955 hom., cov: 32)

Exomes 𝑓: 0.50 ( 181522 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.362

Publications

10 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=-0.89).

BP6

Variant 6-52048442-G-A is Benign according to our data. Variant chr6-52048442-G-A is described in ClinVar as Benign. ClinVar VariationId is 262396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.2407+50C>T		intron_variant	Intron 23 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.2407+50C>T		intron_variant	Intron 23 of 66	1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 link	c.2407+50C>T		intron_variant	Intron 23 of 60	5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62597

AN:

151926

Hom.:

14956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.448

GnomAD2 exomes

AF:

0.476

AC:

119662

AN:

251340

AF XY:

0.470

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.651

Gnomad ASJ exome

AF:

0.497

Gnomad EAS exome

AF:

0.382

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.518

Gnomad OTH exome

AF:

0.511

GnomAD4 exome

AF:

0.498

AC:

706216

AN:

1417894

Hom.:

181522

Cov.:

AF XY:

0.495

AC XY:

350334

AN XY:

708174

show subpopulations

African (AFR)

AF:

0.145

AC:

4759

AN:

32848

American (AMR)

AF:

0.636

AC:

28423

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

12886

AN:

25858

East Asian (EAS)

AF:

0.369

AC:

14582

AN:

39498

South Asian (SAS)

AF:

0.340

AC:

29061

AN:

85416

European-Finnish (FIN)

AF:

0.500

AC:

26666

AN:

53368

Middle Eastern (MID)

AF:

0.424

AC:

2410

AN:

5688

European-Non Finnish (NFE)

AF:

0.522

AC:

559124

AN:

1071582

Other (OTH)

AF:

0.480

AC:

28305

AN:

58956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16795

33591

50386

67182

83977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15634

31268

46902

62536

78170

<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:

0.412

AC:

62599

AN:

152046

Hom.:

14955

Cov.:

AF XY:

0.409

AC XY:

30396

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.159

AC:

6607

AN:

41488

American (AMR)

AF:

0.568

AC:

8687

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

1749

AN:

3472

East Asian (EAS)

AF:

0.382

AC:

1972

AN:

5158

South Asian (SAS)

AF:

0.332

AC:

1599

AN:

4818

European-Finnish (FIN)

AF:

0.472

AC:

4989

AN:

10560

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.523

AC:

35513

AN:

67936

Other (OTH)

AF:

0.444

AC:

939

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1719

3438

5158

6877

8596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.489

Hom.:

25678

Bravo

AF:

0.410

Asia WGS

AF:

0.322

AC:

1123

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

-0.89

CADD

Benign

0.94

(source)

DANN

Benign

0.25

PhyloP100

-0.36

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