rs10498792

Positions:

• chr6-51801833-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.8303-10460A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,146 control chromosomes in the GnomAD database, including 2,044 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 0.15 (2044 hom., cov: 31)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.8303-10460A>G		intron_variant		ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8	c.8303-10460A>G		intron_variant		1	NM_138694.4	ENSP00000360158	P2
PKHD1	ENST00000340994.4	c.8303-10460A>G		intron_variant		5		ENSP00000341097	A2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23336 AN: 152028 Hom.: 2032 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.154 AC: 23386 AN: 152146 Hom.: 2044 Cov.: 31 AF XY: 0.155 AC XY: 11533 AN XY: 74368

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0808

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.150

Alfa AF: 0.113 Hom.: 2365

Bravo AF: 0.154

Asia WGS AF: 0.119 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.83

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: rs10498792; hg19: chr6-51666631; COSMIC: COSV61862547;