Variant 6-51746672-T-C 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.9998+49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,162,188 control chromosomes in the GnomAD database, including 31,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 12094 hom., cov: 32)

Exomes 𝑓: 0.17 ( 19359 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.329

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=-0.78).

BP6

Variant 6-51746672-T-C is Benign according to our data. Variant chr6-51746672-T-C is described in ClinVar as [Benign]. Clinvar id is 262425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 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.9998+49A>G		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.9998+49A>G		intron_variant		1	NM_138694.4	ENSP00000360158.3		P08F94-1
PKHD1	ENST00000340994.4 linkuse as main transcript	c.9998+49A>G		intron_variant		5		ENSP00000341097.4		P08F94-2

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47456

AN:

152008

Hom.:

12049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.709

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.264

GnomAD3 exomes

AF:

0.198

AC:

48680

AN:

245730

Hom.:

7197

AF XY:

0.190

AC XY:

25387

AN XY:

133442

show subpopulations

Gnomad AFR exome

AF:

0.722

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.147

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.170

AC:

171685

AN:

1010062

Hom.:

19359

Cov.:

AF XY:

0.170

AC XY:

88982

AN XY:

522882

show subpopulations

Gnomad4 AFR exome

AF:

0.727

Gnomad4 AMR exome

AF:

0.151

Gnomad4 ASJ exome

AF:

0.192

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.313

AC:

47561

AN:

152126

Hom.:

12094

Cov.:

AF XY:

0.309

AC XY:

22999

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.709

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.164

Hom.:

6387

Bravo

AF:

0.330

Asia WGS

AF:

0.286

AC:

993

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 12, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Polycystic kidney disease 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.9

DANN

Benign

0.86

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