rs6935568

Positions:

• chr6-51822354-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.8302+8507G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 152,222 control chromosomes in the GnomAD database, including 235 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 0.054 (235 hom., cov: 32)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.8302+8507G>A		intron_variant		ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8	c.8302+8507G>A		intron_variant		1	NM_138694.4	ENSP00000360158	P2
PKHD1	ENST00000340994.4	c.8302+8507G>A		intron_variant		5		ENSP00000341097	A2

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8231 AN: 152104 Hom.: 233 Cov.: 32

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0524

Gnomad OTH AF: 0.0459

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

GnomAD4 genome AF: 0.0542 AC: 8255 AN: 152222 Hom.: 235 Cov.: 32 AF XY: 0.0542 AC XY: 4029 AN XY: 74404

Gnomad4 AFR AF: 0.0646

Gnomad4 AMR AF: 0.0366

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.0519

Gnomad4 SAS AF: 0.0705

Gnomad4 FIN AF: 0.0569

Gnomad4 NFE AF: 0.0524

Gnomad4 OTH AF: 0.0487

Alfa AF: 0.0506 Hom.: 287

Bravo AF: 0.0518

Asia WGS AF: 0.0940 AC: 326 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
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: rs6935568; hg19: chr6-51687152;