6-51914840-A-G

Position:

• chr6-51914840-A-G

Variant summary

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

The NM_138694.4(PKHD1):​c.6122-2264T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,858 control chromosomes in the GnomAD database, including 19,908 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 0.49 (19908 hom., cov: 32)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656

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 = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKHD1	NM_138694.4	c.6122-2264T>C		intron_variant		ENST00000371117.8	NP_619639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKHD1	ENST00000371117.8	c.6122-2264T>C		intron_variant		1	NM_138694.4	ENSP00000360158	P2
PKHD1	ENST00000340994.4	c.6122-2264T>C		intron_variant		5		ENSP00000341097	A2

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74335 AN: 151740 Hom.: 19870 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.490 AC: 74421 AN: 151858 Hom.: 19908 Cov.: 32 AF XY: 0.505 AC XY: 37441 AN XY: 74212

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.435

Alfa AF: 0.389 Hom.: 5720

Bravo AF: 0.500

Asia WGS AF: 0.685 AC: 2380 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	0.046
DANN	Benign	0.30

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: rs1266874; hg19: chr6-51779638;