rs116414807

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_138694.4(PKHD1):​c.391-43T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,451,414 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 26 hom., cov: 33)
Exomes 𝑓: 0.0010 ( 16 hom. )

Consequence

PKHD1
NM_138694.4 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.267
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]

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=-0.85).
BP6
Variant 6-52076376-A-T is Benign according to our data. Variant chr6-52076376-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 262402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00859 (1309/152354) while in subpopulation AFR AF= 0.0288 (1197/41574). AF 95% confidence interval is 0.0274. There are 26 homozygotes in gnomad4. There are 572 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PKHD1NM_138694.4 linkuse as main transcriptc.391-43T>A intron_variant ENST00000371117.8 NP_619639.3 P08F94-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PKHD1ENST00000371117.8 linkuse as main transcriptc.391-43T>A intron_variant 1 NM_138694.4 ENSP00000360158.3 P08F94-1
PKHD1ENST00000340994.4 linkuse as main transcriptc.391-43T>A intron_variant 5 ENSP00000341097.4 P08F94-2

Frequencies

GnomAD3 genomes
AF:
0.00861
AC:
1310
AN:
152236
Hom.:
26
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0289
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00517
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00812
GnomAD3 exomes
AF:
0.00241
AC:
603
AN:
250190
Hom.:
11
AF XY:
0.00173
AC XY:
234
AN XY:
135272
show subpopulations
Gnomad AFR exome
AF:
0.0285
Gnomad AMR exome
AF:
0.00255
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000655
Gnomad FIN exome
AF:
0.0000929
Gnomad NFE exome
AF:
0.000336
Gnomad OTH exome
AF:
0.00197
GnomAD4 exome
AF:
0.00103
AC:
1340
AN:
1299060
Hom.:
16
Cov.:
20
AF XY:
0.000922
AC XY:
604
AN XY:
655214
show subpopulations
Gnomad4 AFR exome
AF:
0.0270
Gnomad4 AMR exome
AF:
0.00315
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000241
Gnomad4 FIN exome
AF:
0.0000563
Gnomad4 NFE exome
AF:
0.000233
Gnomad4 OTH exome
AF:
0.00222
GnomAD4 genome
AF:
0.00859
AC:
1309
AN:
152354
Hom.:
26
Cov.:
33
AF XY:
0.00768
AC XY:
572
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.0288
Gnomad4 AMR
AF:
0.00516
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00803
Alfa
AF:
0.00423
Hom.:
0
Bravo
AF:
0.00983
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Feb 01, 2017- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -
Autosomal recessive polycystic kidney disease Benign:1
Benign, no assertion criteria providedclinical testingNatera, Inc.Apr 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.96
DANN
Benign
0.59

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.

Other links and lift over

dbSNP: rs116414807; hg19: chr6-51941174; API