rs1414503

Positions:

• chr6-51657690-G-C

Variant summary

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

The NM_138694.4(PKHD1):​c.11174+1262C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,962 control chromosomes in the GnomAD database, including 4,376 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 0.21 (4376 hom., cov: 32)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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]

LOC124900615 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKHD1	NM_138694.4	c.11174+1262C>G		intron_variant		ENST00000371117.8
LOC124900615	XR_926871.3	n.155+5317G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKHD1	ENST00000371117.8	c.11174+1262C>G		intron_variant		1	NM_138694.4	P2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32333 AN: 151844 Hom.: 4374 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.213 AC: 32361 AN: 151962 Hom.: 4376 Cov.: 32 AF XY: 0.214 AC XY: 15883 AN XY: 74274

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.204

Alfa AF: 0.175 Hom.: 400

Bravo AF: 0.235

Asia WGS AF: 0.269 AC: 932 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.56

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: rs1414503; hg19: chr6-51522488;