rs547420704

chr6-52024539-TAAAG-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_138694.4(PKHD1):c.5236+31_5236+34del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00638 in 1,590,448 control chromosomes in the GnomAD database, including 53 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (52 hom.)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.464

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.

• BP6: Variant 6-52024539-TAAAG-T is Benign according to our data. Variant chr6-52024539-TAAAG-T is described in ClinVar as [Likely_benign]. Clinvar id is 262405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKHD1	NM_138694.4	c.5236+31_5236+34del		intron_variant		ENST00000371117.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKHD1	ENST00000371117.8	c.5236+31_5236+34del		intron_variant		1	NM_138694.4	P2
PKHD1	ENST00000340994.4	c.5236+31_5236+34del		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.00428 AC: 652 AN: 152228 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00772

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00661

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00445 AC: 1096 AN: 246460 Hom.: 6 AF XY: 0.00440 AC XY: 591 AN XY: 134264

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00501

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000719

Gnomad FIN exome AF: 0.00729

Gnomad NFE exome AF: 0.00693

Gnomad OTH exome AF: 0.00597

GnomAD4 exome AF: 0.00661 AC: 9503 AN: 1438102 Hom.: 52 AF XY: 0.00635 AC XY: 4551 AN XY: 716966

Gnomad4 AFR exome AF: 0.00109

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.00462

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000899

Gnomad4 FIN exome AF: 0.00733

Gnomad4 NFE exome AF: 0.00776

Gnomad4 OTH exome AF: 0.00595

GnomAD4 genome AF: 0.00428 AC: 652 AN: 152346 Hom.: 1 Cov.: 32 AF XY: 0.00391 AC XY: 291 AN XY: 74498

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00772

Gnomad4 NFE AF: 0.00661

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00476 Hom.: 0

Bravo AF: 0.00352

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

Autosomal recessive polycystic kidney disease Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Counsyl

Oct 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

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: rs547420704; hg19: chr6-51889337;