rs9382044

chr6-51867830-G-Achr6-51867830-G-C

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.7733+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,597,854 control chromosomes in the GnomAD database, including 114,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13527 hom., cov: 33)
  • Exomes 𝑓: 0.35 (101390 hom.)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.00600

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=-0.87).
• BP6: Variant 6-51867830-G-A is Benign according to our data. Variant chr6-51867830-G-A is described in ClinVar as [Benign]. Clinvar id is 262412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKHD1	NM_138694.4	c.7733+33C>T		intron_variant		ENST00000371117.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKHD1	ENST00000371117.8	c.7733+33C>T		intron_variant		1	NM_138694.4	P2
PKHD1	ENST00000340994.4	c.7733+33C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61171 AN: 151898 Hom.: 13518 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.368

GnomAD3 exomes AF: 0.446 AC: 110795 AN: 248648 Hom.: 28719 AF XY: 0.436 AC XY: 58731 AN XY: 134718

Gnomad AFR exome AF: 0.435

Gnomad AMR exome AF: 0.654

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.868

Gnomad SAS exome AF: 0.517

Gnomad FIN exome AF: 0.450

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.372

GnomAD4 exome AF: 0.355 AC: 512612 AN: 1445838 Hom.: 101390 Cov.: 29 AF XY: 0.358 AC XY: 257772 AN XY: 720194

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.828

Gnomad4 SAS exome AF: 0.514

Gnomad4 FIN exome AF: 0.436

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.403 AC: 61210 AN: 152016 Hom.: 13527 Cov.: 33 AF XY: 0.418 AC XY: 31048 AN XY: 74312

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.366

Alfa AF: 0.342 Hom.: 1956

Bravo AF: 0.407

Asia WGS AF: 0.622 AC: 2163 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Polycystic kidney disease 4 Benign:2

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not specified Benign:1

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 12, 2018

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.5
Dann	Benign	0.77

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: rs9382044; hg19: chr6-51732628; COSMIC: COSV61899865;