Variant 6-51934368-T-C 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.5909-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,216,254 control chromosomes in the GnomAD database, including 281,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38157 hom., cov: 32)

Exomes 𝑓: 0.67 ( 243549 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.578

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:

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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=-0.86).

BP6

Variant 6-51934368-T-C is Benign according to our data. Variant chr6-51934368-T-C is described in ClinVar as [Benign]. Clinvar id is 262406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 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.5909-46A>G		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.5909-46A>G		intron_variant		1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 linkuse as main transcript	c.5909-46A>G		intron_variant		5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.703

AC:

106930

AN:

152002

Hom.:

38114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.736

Gnomad ASJ

AF:

0.514

Gnomad EAS

AF:

0.941

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.741

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.646

Gnomad OTH

AF:

0.640

GnomAD3 exomes

AF:

0.706

AC:

173908

AN:

246412

Hom.:

62519

AF XY:

0.696

AC XY:

92815

AN XY:

133290

show subpopulations

Gnomad AFR exome

AF:

0.774

Gnomad AMR exome

AF:

0.811

Gnomad ASJ exome

AF:

0.518

Gnomad EAS exome

AF:

0.942

Gnomad SAS exome

AF:

0.712

Gnomad FIN exome

AF:

0.735

Gnomad NFE exome

AF:

0.637

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.670

AC:

713082

AN:

1064134

Hom.:

243549

Cov.:

AF XY:

0.669

AC XY:

366912

AN XY:

548196

show subpopulations

Gnomad4 AFR exome

AF:

0.764

Gnomad4 AMR exome

AF:

0.802

Gnomad4 ASJ exome

AF:

0.510

Gnomad4 EAS exome

AF:

0.931

Gnomad4 SAS exome

AF:

0.708

Gnomad4 FIN exome

AF:

0.735

Gnomad4 NFE exome

AF:

0.644

Gnomad4 OTH exome

AF:

0.658

GnomAD4 genome

AF:

0.704

AC:

107029

AN:

152120

Hom.:

38157

Cov.:

AF XY:

0.711

AC XY:

52878

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.770

Gnomad4 AMR

AF:

0.737

Gnomad4 ASJ

AF:

0.514

Gnomad4 EAS

AF:

0.941

Gnomad4 SAS

AF:

0.721

Gnomad4 FIN

AF:

0.741

Gnomad4 NFE

AF:

0.646

Gnomad4 OTH

AF:

0.640

Alfa

AF:

0.646

Hom.:

54920

Bravo

AF:

0.705

Asia WGS

AF:

0.811

AC:

2821

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

-0.86

CADD

Benign

6.2

DANN

Benign

0.62

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