dbSNP rs10498792: PKHD1:c.8303-10460A>G (chr6-51801833-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138694.4(PKHD1):c.8303-10460A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,146 control chromosomes in the GnomAD database, including 2,044 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2044 hom., cov: 31)

Consequence

PKHD1
NM_138694.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.126

Publications

25 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive polycystic kidney disease
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Orphanet
polycystic kidney disease 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Genomics England PanelApp
Caroli disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PKHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKHD1	NM_138694.4 link	c.8303-10460A>G		intron_variant	Intron 52 of 66	ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8 link	c.8303-10460A>G		intron_variant	Intron 52 of 66	1	NM_138694.4	ENSP00000360158.3
PKHD1	ENST00000340994.4 link	c.8303-10460A>G		intron_variant	Intron 52 of 60	5		ENSP00000341097.4

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23336

AN:

152028

Hom.:

2032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.0814

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.154

AC:

23386

AN:

152146

Hom.:

2044

Cov.:

AF XY:

0.155

AC XY:

11533

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.238

AC:

9881

AN:

41518

American (AMR)

AF:

0.136

AC:

2075

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3464

East Asian (EAS)

AF:

0.142

AC:

733

AN:

5178

South Asian (SAS)

AF:

0.0808

AC:

390

AN:

4824

European-Finnish (FIN)

AF:

0.173

AC:

1833

AN:

10566

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7640

AN:

68006

Other (OTH)

AF:

0.150

AC:

316

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

1016

2032

3048

4064

5080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.120

Hom.:

5255

Bravo

AF:

0.154

Asia WGS

AF:

0.119

AC:

415

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over