chr6-52026213-T-C

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.3629-32A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,595,544 control chromosomes in the GnomAD database, including 233,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.46 ( 17856 hom., cov: 32)

Exomes 𝑓: 0.54 ( 215935 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.291

Publications

11 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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-52026213-T-C is Benign according to our data. Variant chr6-52026213-T-C is described in CliVar as Benign. Clinvar id is 262399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52026213-T-C is described in CliVar as Benign. Clinvar id is 262399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52026213-T-C is described in CliVar as Benign. Clinvar id is 262399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-52026213-T-C is described in CliVar as Benign. Clinvar id is 262399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.3629-32A>G		intron_variant	Intron 31 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.3629-32A>G		intron_variant	Intron 31 of 66	1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 link	c.3629-32A>G		intron_variant	Intron 31 of 60	5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70544

AN:

151936

Hom.:

17854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.480

GnomAD2 exomes

AF:

0.518

AC:

126193

AN:

243558

AF XY:

0.514

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.668

Gnomad ASJ exome

AF:

0.504

Gnomad EAS exome

AF:

0.364

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.558

Gnomad OTH exome

AF:

0.539

GnomAD4 exome

AF:

0.542

AC:

782252

AN:

1443490

Hom.:

215935

Cov.:

AF XY:

0.540

AC XY:

388383

AN XY:

719374

show subpopulations

African (AFR)

AF:

0.255

AC:

8428

AN:

33040

American (AMR)

AF:

0.654

AC:

29224

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

13163

AN:

26034

East Asian (EAS)

AF:

0.329

AC:

13010

AN:

39588

South Asian (SAS)

AF:

0.449

AC:

38542

AN:

85820

European-Finnish (FIN)

AF:

0.510

AC:

27032

AN:

52996

Middle Eastern (MID)

AF:

0.467

AC:

2673

AN:

5718

European-Non Finnish (NFE)

AF:

0.565

AC:

619208

AN:

1095900

Other (OTH)

AF:

0.519

AC:

30972

AN:

59716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

18545

37091

55636

74182

92727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17062

34124

51186

68248

85310

<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:

0.464

AC:

70569

AN:

152054

Hom.:

17856

Cov.:

AF XY:

0.461

AC XY:

34248

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.266

AC:

11050

AN:

41478

American (AMR)

AF:

0.586

AC:

8962

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1769

AN:

3470

East Asian (EAS)

AF:

0.357

AC:

1842

AN:

5158

South Asian (SAS)

AF:

0.438

AC:

2112

AN:

4818

European-Finnish (FIN)

AF:

0.478

AC:

5046

AN:

10562

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.560

AC:

38058

AN:

67966

Other (OTH)

AF:

0.477

AC:

1007

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1829

3658

5486

7315

9144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.447

Hom.:

2856

Bravo

AF:

0.465

Asia WGS

AF:

0.373

AC:

1301

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

Jun 19, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou 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

-0.85

CADD

Benign

7.5

(source)

DANN

Benign

0.59

PhyloP100

0.29

BranchPoint Hunter

3.0

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