rs728996

chr6-51778216-C-T

Variant summary

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

The NM_138694.4(PKHD1):c.8441-2295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,936 control chromosomes in the GnomAD database, including 25,914 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 0.57 (25914 hom., cov: 32)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKHD1	NM_138694.4	c.8441-2295G>A		intron_variant		ENST00000371117.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKHD1	ENST00000371117.8	c.8441-2295G>A		intron_variant		1	NM_138694.4	P2
PKHD1	ENST00000340994.4	c.8441-2295G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86868 AN: 151818 Hom.: 25918 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.572 AC: 86882 AN: 151936 Hom.: 25914 Cov.: 32 AF XY: 0.580 AC XY: 43046 AN XY: 74228

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.566

Alfa AF: 0.581 Hom.: 5526

Bravo AF: 0.561

Asia WGS AF: 0.724 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.0040
Dann	Benign	0.60

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: rs728996; hg19: chr6-51643014;