rs1326581

Positions:

• chr6-51806363-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138694.4(PKHD1):​c.8303-14990T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,020 control chromosomes in the GnomAD database, including 27,559 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (27559 hom., cov: 32)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.8303-14990T>C		intron_variant		ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8	c.8303-14990T>C		intron_variant		1	NM_138694.4	ENSP00000360158	P2
PKHD1	ENST00000340994.4	c.8303-14990T>C		intron_variant		5		ENSP00000341097	A2

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90810 AN: 151902 Hom.: 27560 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.596

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.598 AC: 90837 AN: 152020 Hom.: 27559 Cov.: 32 AF XY: 0.603 AC XY: 44803 AN XY: 74310

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.591

Alfa AF: 0.621 Hom.: 10384

Bravo AF: 0.597

Asia WGS AF: 0.661 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.2
DANN	Benign	0.79

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: rs1326581; hg19: chr6-51671161;