rs12529717

chr6-51830843-T-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.8302+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,609,690 control chromosomes in the GnomAD database, including 2,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (224 hom., cov: 32)
  • Exomes 𝑓: 0.050 (2133 hom.)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.627

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=-0.92).
• BP6: Variant 6-51830843-T-C is Benign according to our data. Variant chr6-51830843-T-C is described in ClinVar as [Benign]. Clinvar id is 96430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKHD1	NM_138694.4	c.8302+18A>G		intron_variant		ENST00000371117.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKHD1	ENST00000371117.8	c.8302+18A>G		intron_variant		1	NM_138694.4	P2
PKHD1	ENST00000340994.4	c.8302+18A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.0529 AC: 8051 AN: 152098 Hom.: 223 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0362

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0523

Gnomad OTH AF: 0.0430

GnomAD3 exomes AF: 0.0522 AC: 13110 AN: 251020 Hom.: 394 AF XY: 0.0527 AC XY: 7145 AN XY: 135676

Gnomad AFR exome AF: 0.0606

Gnomad AMR exome AF: 0.0400

Gnomad ASJ exome AF: 0.0360

Gnomad EAS exome AF: 0.0332

Gnomad SAS exome AF: 0.0774

Gnomad FIN exome AF: 0.0582

Gnomad NFE exome AF: 0.0509

Gnomad OTH exome AF: 0.0602

GnomAD4 exome AF: 0.0505 AC: 73588 AN: 1457474 Hom.: 2133 Cov.: 28 AF XY: 0.0513 AC XY: 37231 AN XY: 725268

Gnomad4 AFR exome AF: 0.0601

Gnomad4 AMR exome AF: 0.0402

Gnomad4 ASJ exome AF: 0.0380

Gnomad4 EAS exome AF: 0.0836

Gnomad4 SAS exome AF: 0.0733

Gnomad4 FIN exome AF: 0.0568

Gnomad4 NFE exome AF: 0.0479

Gnomad4 OTH exome AF: 0.0485

GnomAD4 genome AF: 0.0530 AC: 8070 AN: 152216 Hom.: 224 Cov.: 32 AF XY: 0.0530 AC XY: 3943 AN XY: 74414

Gnomad4 AFR AF: 0.0602

Gnomad4 AMR AF: 0.0363

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.0527

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.0566

Gnomad4 NFE AF: 0.0523

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.0566 Hom.: 53

Bravo AF: 0.0502

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 04, 2016	- -

Autosomal recessive polycystic kidney disease Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 13, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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	-0.92
Cadd	Benign	0.30
Dann	Benign	0.40

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

Other links and lift over

dbSNP: rs12529717; hg19: chr6-51695641; COSMIC: COSV61872443;