rs1571084

Positions:

chr6-51830849-A-T

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+12T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,609,244 control chromosomes in the GnomAD database, including 143,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16090 hom., cov: 32)

Exomes 𝑓: 0.41 ( 127005 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.317

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

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 6-51830849-A-T is Benign according to our data. Variant chr6-51830849-A-T is described in ClinVar as [Benign]. Clinvar id is 96429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-51830849-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 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.8302+12T>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.8302+12T>A		intron_variant		1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 linkuse as main transcript	c.8302+12T>A		intron_variant		5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.444

AC:

67445

AN:

151822

Hom.:

16065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.0830

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.479

GnomAD3 exomes

AF:

0.375

AC:

94101

AN:

250980

Hom.:

19966

AF XY:

0.378

AC XY:

51247

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.590

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.0823

Gnomad SAS exome

AF:

0.308

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.440

Gnomad OTH exome

AF:

0.424

GnomAD4 exome

AF:

0.409

AC:

596261

AN:

1457304

Hom.:

127005

Cov.:

AF XY:

0.407

AC XY:

294944

AN XY:

725232

show subpopulations

Gnomad4 AFR exome

AF:

0.600

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.553

Gnomad4 EAS exome

AF:

0.0849

Gnomad4 SAS exome

AF:

0.312

Gnomad4 FIN exome

AF:

0.350

Gnomad4 NFE exome

AF:

0.427

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.444

AC:

67518

AN:

151940

Hom.:

16090

Cov.:

AF XY:

0.434

AC XY:

32257

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.587

Gnomad4 AMR

AF:

0.337

Gnomad4 ASJ

AF:

0.563

Gnomad4 EAS

AF:

0.0829

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.477

Alfa

AF:

0.443

Hom.:

2885

Bravo

AF:

0.456

Asia WGS

AF:

0.259

AC:

901

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive polycystic kidney disease

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 12, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 27, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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	- -

Polycystic kidney disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

The c.8302+12T>A, p.? variant was identified in 38.61% of 46763 control alleles in the Exome Aggregation Consortium (March 14, 2016). According to ACMG guidelines for variant classification based on allele frequency, category BA1, this variant is considered benign and has not been further reviewed (Richards 2015). -

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

-0.95

CADD

Benign

0.89

DANN

Benign

0.45

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