rs58823342

chr6-51753157-T-Cchr6-51753157-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138694.4(PKHD1):c.8950+44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,565,510 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (79 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (69 hom.)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.201

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-51753157-T-C is Benign according to our data. Variant chr6-51753157-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 262424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.059 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKHD1	NM_138694.4	c.8950+44A>G		intron_variant		ENST00000371117.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKHD1	ENST00000371117.8	c.8950+44A>G		intron_variant		1	NM_138694.4	P2
PKHD1	ENST00000340994.4	c.8950+44A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2720 AN: 152212 Hom.: 79 Cov.: 33

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0119

GnomAD3 exomes AF: 0.00526 AC: 1308 AN: 248872 Hom.: 31 AF XY: 0.00381 AC XY: 513 AN XY: 134550

Gnomad AFR exome AF: 0.0660

Gnomad AMR exome AF: 0.00494

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000391

Gnomad OTH exome AF: 0.00348

GnomAD4 exome AF: 0.00197 AC: 2777 AN: 1413180 Hom.: 69 Cov.: 25 AF XY: 0.00172 AC XY: 1212 AN XY: 704632

Gnomad4 AFR exome AF: 0.0613

Gnomad4 AMR exome AF: 0.00575

Gnomad4 ASJ exome AF: 0.0000778

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000200

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000222

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.0179 AC: 2720 AN: 152330 Hom.: 79 Cov.: 33 AF XY: 0.0176 AC XY: 1312 AN XY: 74500

Gnomad4 AFR AF: 0.0610

Gnomad4 AMR AF: 0.00863

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00938 Hom.: 9

Bravo AF: 0.0214

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely 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 13, 2018

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.58
Dann	Benign	0.53

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

Other links and lift over

dbSNP: rs58823342; hg19: chr6-51617955;