Variant rs10948667 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.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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.2407+50C>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 link	c.2407+50C>T		intron_variant		1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 link	c.2407+50C>T		intron_variant		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

GnomAD3 exomes

AF:

0.476

AC:

119662

AN:

251340

Hom.:

30617

AF XY:

0.470

AC XY:

63833

AN XY:

135840

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 SAS exome

AF:

0.337

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

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.636

Gnomad4 ASJ exome

AF:

0.498

Gnomad4 EAS exome

AF:

0.369

Gnomad4 SAS exome

AF:

0.340

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.522

Gnomad4 OTH exome

AF:

0.480

GnomAD4 genome

AF:

0.412

AC:

62599

AN:

152046

Hom.:

14955

Cov.:

AF XY:

0.409

AC XY:

30396

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.568

Gnomad4 ASJ

AF:

0.504

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.523

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.500

Hom.:

20309

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

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

-0.89

CADD

Benign

0.94

DANN

Benign

0.25

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