Variant 6-51775953-C-G 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.8441-32G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 984,000 control chromosomes in the GnomAD database, including 91,448 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 0.34 ( 11127 hom., cov: 32)

Exomes 𝑓: 0.43 ( 80321 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.770

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-51775953-C-G is Benign according to our data. Variant chr6-51775953-C-G is described in ClinVar as [Benign]. Clinvar id is 262421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 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.8441-32G>C		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.8441-32G>C		intron_variant		1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 linkuse as main transcript	c.8441-32G>C		intron_variant		5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52305

AN:

151508

Hom.:

11132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.414

Gnomad OTH

AF:

0.345

GnomAD3 exomes

AF:

0.445

AC:

107151

AN:

240598

Hom.:

26225

AF XY:

0.449

AC XY:

58600

AN XY:

130612

show subpopulations

Gnomad AFR exome

AF:

0.0935

Gnomad AMR exome

AF:

0.589

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.704

Gnomad SAS exome

AF:

0.520

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.428

AC:

356043

AN:

832374

Hom.:

80321

Cov.:

AF XY:

0.432

AC XY:

189971

AN XY:

440000

show subpopulations

Gnomad4 AFR exome

AF:

0.0913

Gnomad4 AMR exome

AF:

0.571

Gnomad4 ASJ exome

AF:

0.318

Gnomad4 EAS exome

AF:

0.633

Gnomad4 SAS exome

AF:

0.521

Gnomad4 FIN exome

AF:

0.435

Gnomad4 NFE exome

AF:

0.410

Gnomad4 OTH exome

AF:

0.399

GnomAD4 genome

AF:

0.345

AC:

52290

AN:

151626

Hom.:

11127

Cov.:

AF XY:

0.355

AC XY:

26282

AN XY:

74062

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.478

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.674

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.436

Gnomad4 NFE

AF:

0.413

Gnomad4 OTH

AF:

0.341

Alfa

AF:

0.373

Hom.:

2118

Bravo

AF:

0.334

Asia WGS

AF:

0.506

AC:

1754

AN:

3466

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

-0.81

CADD

Benign

0.30

DANN

Benign

0.71

BranchPoint Hunter

2.0

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