Variant rs12527920 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.8174-49G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 1,441,370 control chromosomes in the GnomAD database, including 2,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 240 hom., cov: 32)

Exomes 𝑓: 0.051 ( 1960 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.774

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=-0.84).

BP6

Variant 6-51831038-C-G is Benign according to our data. Variant chr6-51831038-C-G is described in ClinVar as [Benign]. Clinvar id is 262420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0662 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.8174-49G>C		intron_variant		ENST00000371117.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKHD1	ENST00000371117.8 linkuse as main transcript	c.8174-49G>C		intron_variant		1	NM_138694.4	P2	P08F94-1
PKHD1	ENST00000340994.4 linkuse as main transcript	c.8174-49G>C		intron_variant		5		A2	P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.0545

AC:

8296

AN:

152092

Hom.:

236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0654

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.0524

Gnomad SAS

AF:

0.0726

Gnomad FIN

AF:

0.0571

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0524

Gnomad OTH

AF:

0.0455

GnomAD3 exomes

AF:

0.0532

AC:

11776

AN:

221222

Hom.:

344

AF XY:

0.0536

AC XY:

6438

AN XY:

120046

show subpopulations

Gnomad AFR exome

AF:

0.0666

Gnomad AMR exome

AF:

0.0402

Gnomad ASJ exome

AF:

0.0356

Gnomad EAS exome

AF:

0.0344

Gnomad SAS exome

AF:

0.0772

Gnomad FIN exome

AF:

0.0585

Gnomad NFE exome

AF:

0.0519

Gnomad OTH exome

AF:

0.0606

GnomAD4 exome

AF:

0.0513

AC:

66114

AN:

1289160

Hom.:

1960

Cov.:

AF XY:

0.0522

AC XY:

33854

AN XY:

649146

show subpopulations

Gnomad4 AFR exome

AF:

0.0667

Gnomad4 AMR exome

AF:

0.0401

Gnomad4 ASJ exome

AF:

0.0379

Gnomad4 EAS exome

AF:

0.0849

Gnomad4 SAS exome

AF:

0.0733

Gnomad4 FIN exome

AF:

0.0568

Gnomad4 NFE exome

AF:

0.0484

Gnomad4 OTH exome

AF:

0.0493

GnomAD4 genome

AF:

0.0547

AC:

8327

AN:

152210

Hom.:

240

Cov.:

AF XY:

0.0548

AC XY:

4079

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0656

Gnomad4 AMR

AF:

0.0370

Gnomad4 ASJ

AF:

0.0349

Gnomad4 EAS

AF:

0.0530

Gnomad4 SAS

AF:

0.0725

Gnomad4 FIN

AF:

0.0571

Gnomad4 NFE

AF:

0.0524

Gnomad4 OTH

AF:

0.0483

Alfa

AF:

0.0571

Hom.:

Bravo

AF:

0.0522

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 13, 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

-0.84

CADD

Benign

2.2

DANN

Benign

0.66

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