rs1571084

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

2

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]

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 UniProt
PKHD1NM_138694.4 linkuse as main transcriptc.8302+12T>A intron_variant ENST00000371117.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PKHD1ENST00000371117.8 linkuse as main transcriptc.8302+12T>A intron_variant 1 NM_138694.4 P2P08F94-1
PKHD1ENST00000340994.4 linkuse as main transcriptc.8302+12T>A intron_variant 5 A2P08F94-2

Frequencies

GnomAD3 genomes
AF:
0.444
AC:
67445
AN:
151822
Hom.:
16065
Cov.:
32
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.:
31
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.:
32
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, no assertion criteria providedclinical testingNatera, Inc.Apr 12, 2018- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 submitterclinical testingInvitaeFeb 01, 2024- -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Oct 27, 2015- -
Polycystic kidney disease 4 Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
Benign, criteria provided, single submitterclinical testingPars Genome LabJun 19, 2021- -
Polycystic kidney disease Benign:1
Benign, no assertion criteria providedclinical testingDepartment 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 submitterclinical testingGeneDxJul 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.

Other links and lift over

dbSNP: rs1571084; hg19: chr6-51695647; COSMIC: COSV61861095; API