dbSNP rs2174860: PKHD1:c.11507-21A>G (chr6-51632744-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138694.4(PKHD1):c.11507-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 1,598,530 control chromosomes in the GnomAD database, including 965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 234 hom., cov: 32)

Exomes 𝑓: 0.028 ( 731 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.80

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:

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=-0.92).

BP6

Variant 6-51632744-T-C is Benign according to our data. Variant chr6-51632744-T-C is described in ClinVar as [Benign]. Clinvar id is 262385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.11507-21A>G		intron_variant	Intron 64 of 66	ENST00000371117.8	NP_619639.3	P08F94-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8 link	c.11507-21A>G		intron_variant	Intron 64 of 66	1	NM_138694.4	ENSP00000360158.3		P08F94-1

Frequencies

GnomAD3 genomes

AF:

0.0427

AC:

6492

AN:

151942

Hom.:

233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0927

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0268

Gnomad OTH

AF:

0.0383

GnomAD3 exomes

AF:

0.0273

AC:

6821

AN:

250118

Hom.:

145

AF XY:

0.0262

AC XY:

3536

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.0940

Gnomad AMR exome

AF:

0.0291

Gnomad ASJ exome

AF:

0.0286

Gnomad EAS exome

AF:

0.000328

Gnomad SAS exome

AF:

0.0198

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.0267

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0275

AC:

39795

AN:

1446470

Hom.:

731

Cov.:

AF XY:

0.0270

AC XY:

19435

AN XY:

720832

show subpopulations

Gnomad4 AFR exome

AF:

0.0955

Gnomad4 AMR exome

AF:

0.0291

Gnomad4 ASJ exome

AF:

0.0274

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.0202

Gnomad4 FIN exome

AF:

0.0138

Gnomad4 NFE exome

AF:

0.0277

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0428

AC:

6502

AN:

152060

Hom.:

234

Cov.:

AF XY:

0.0413

AC XY:

3069

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0926

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.0106

Gnomad4 NFE

AF:

0.0269

Gnomad4 OTH

AF:

0.0379

Alfa

AF:

0.0329

Hom.:

Bravo

AF:

0.0470

Asia WGS

AF:

0.0180

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive polycystic kidney disease

Benign:1

Apr 13, 2018

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Jul 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0090

DANN

Benign

0.28

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