Variant rs12529717 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.8302+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,609,690 control chromosomes in the GnomAD database, including 2,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 224 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2133 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.627

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=-0.92).

BP6

Variant 6-51830843-T-C is Benign according to our data. Variant chr6-51830843-T-C is described in ClinVar as [Benign]. Clinvar id is 96430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKHD1	NM_138694.4 linkuse as main transcript	c.8302+18A>G		intron_variant		ENST00000371117.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKHD1	ENST00000371117.8 linkuse as main transcript	c.8302+18A>G		intron_variant		1	NM_138694.4	P2	P08F94-1
PKHD1	ENST00000340994.4 linkuse as main transcript	c.8302+18A>G		intron_variant		5		A2	P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.0529

AC:

8051

AN:

152098

Hom.:

223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.0522

Gnomad SAS

AF:

0.0727

Gnomad FIN

AF:

0.0566

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0523

Gnomad OTH

AF:

0.0430

GnomAD3 exomes

AF:

0.0522

AC:

13110

AN:

251020

Hom.:

394

AF XY:

0.0527

AC XY:

7145

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.0606

Gnomad AMR exome

AF:

0.0400

Gnomad ASJ exome

AF:

0.0360

Gnomad EAS exome

AF:

0.0332

Gnomad SAS exome

AF:

0.0774

Gnomad FIN exome

AF:

0.0582

Gnomad NFE exome

AF:

0.0509

Gnomad OTH exome

AF:

0.0602

GnomAD4 exome

AF:

0.0505

AC:

73588

AN:

1457474

Hom.:

2133

Cov.:

AF XY:

0.0513

AC XY:

37231

AN XY:

725268

show subpopulations

Gnomad4 AFR exome

AF:

0.0601

Gnomad4 AMR exome

AF:

0.0402

Gnomad4 ASJ exome

AF:

0.0380

Gnomad4 EAS exome

AF:

0.0836

Gnomad4 SAS exome

AF:

0.0733

Gnomad4 FIN exome

AF:

0.0568

Gnomad4 NFE exome

AF:

0.0479

Gnomad4 OTH exome

AF:

0.0485

GnomAD4 genome

AF:

0.0530

AC:

8070

AN:

152216

Hom.:

224

Cov.:

AF XY:

0.0530

AC XY:

3943

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0602

Gnomad4 AMR

AF:

0.0363

Gnomad4 ASJ

AF:

0.0349

Gnomad4 EAS

AF:

0.0527

Gnomad4 SAS

AF:

0.0726

Gnomad4 FIN

AF:

0.0566

Gnomad4 NFE

AF:

0.0523

Gnomad4 OTH

AF:

0.0459

Alfa

AF:

0.0566

Hom.:

Bravo

AF:

0.0502

Asia WGS

AF:

0.0960

AC:

332

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 04, 2016	- -

Autosomal recessive polycystic kidney disease

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 13, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

-0.92

CADD

Benign

0.30

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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