6-51757651-T-C

Variant summary

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

The NM_138694.4(PKHD1):c.8643-2713A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,838 control chromosomes in the GnomAD database, including 22,717 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 0.54 (22717 hom., cov: 30)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKHD1	NM_138694.4	c.8643-2713A>G		intron_variant		ENST00000371117.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKHD1	ENST00000371117.8	c.8643-2713A>G		intron_variant		1	NM_138694.4	P2
PKHD1	ENST00000340994.4	c.8643-2713A>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81233 AN: 151720 Hom.: 22711 Cov.: 30

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.535 AC: 81271 AN: 151838 Hom.: 22717 Cov.: 30 AF XY: 0.545 AC XY: 40464 AN XY: 74182

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.542

Alfa AF: 0.550 Hom.: 14940

Bravo AF: 0.527

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.46
Dann	Benign	0.51

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: rs2025751; hg19: chr6-51622449;