Variant rs12523900 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.8173+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 1,346,820 control chromosomes in the GnomAD database, including 2,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 231 hom., cov: 32)

Exomes 𝑓: 0.051 ( 1816 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.454

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=-0.88).

BP6

Variant 6-51836367-C-T is Benign according to our data. Variant chr6-51836367-C-T is described in ClinVar as [Benign]. Clinvar id is 262419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0682 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.8173+37G>A		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.8173+37G>A		intron_variant		1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 linkuse as main transcript	c.8173+37G>A		intron_variant		5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.0537

AC:

8166

AN:

152014

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0365

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.0515

Gnomad SAS

AF:

0.0747

Gnomad FIN

AF:

0.0566

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0509

Gnomad OTH

AF:

0.0449

GnomAD3 exomes

AF:

0.0517

AC:

12968

AN:

250844

Hom.:

383

AF XY:

0.0519

AC XY:

7042

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.0657

Gnomad AMR exome

AF:

0.0403

Gnomad ASJ exome

AF:

0.0320

Gnomad EAS exome

AF:

0.0327

Gnomad SAS exome

AF:

0.0768

Gnomad FIN exome

AF:

0.0575

Gnomad NFE exome

AF:

0.0497

Gnomad OTH exome

AF:

0.0595

GnomAD4 exome

AF:

0.0507

AC:

60580

AN:

1194690

Hom.:

1816

Cov.:

AF XY:

0.0515

AC XY:

31321

AN XY:

607924

show subpopulations

Gnomad4 AFR exome

AF:

0.0672

Gnomad4 AMR exome

AF:

0.0405

Gnomad4 ASJ exome

AF:

0.0335

Gnomad4 EAS exome

AF:

0.0848

Gnomad4 SAS exome

AF:

0.0733

Gnomad4 FIN exome

AF:

0.0561

Gnomad4 NFE exome

AF:

0.0475

Gnomad4 OTH exome

AF:

0.0486

GnomAD4 genome

AF:

0.0539

AC:

8195

AN:

152130

Hom.:

231

Cov.:

AF XY:

0.0540

AC XY:

4017

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0655

Gnomad4 AMR

AF:

0.0365

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.0520

Gnomad4 SAS

AF:

0.0745

Gnomad4 FIN

AF:

0.0566

Gnomad4 NFE

AF:

0.0509

Gnomad4 OTH

AF:

0.0478

Alfa

AF:

0.0534

Hom.:

Bravo

AF:

0.0514

Asia WGS

AF:

0.0990

AC:

343

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

-0.88

CADD

Benign

1.3

DANN

Benign

0.64

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