rs9382044

Variant names:

• chr6-51867830-G-A
• rs9382044
• NM_138694.4:c.7733+33C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-51867830-G-A
• chr6-51867830-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138694.4(PKHD1):​c.7733+33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,597,854 control chromosomes in the GnomAD database, including 114,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13527 hom., cov: 33)
  • Exomes 𝑓: 0.35 (101390 hom.)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.00600
• Publications: 8 publications found

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]

PKHD1 Gene-Disease associations (from GenCC):

• autosomal recessive polycystic kidney disease

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Orphanet
• polycystic kidney disease 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Caroli disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-51867830-G-A is Benign according to our data. Variant chr6-51867830-G-A is described in ClinVar as Benign. ClinVar VariationId is 262412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138694.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKHD1	NM_138694.4	MANE Select	c.7733+33C>T		intron	N/A	NP_619639.3
	PKHD1	NM_170724.3		c.7733+33C>T		intron	N/A	NP_733842.2	P08F94-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKHD1	ENST00000371117.8	TSL:1 MANE Select	c.7733+33C>T		intron	N/A	ENSP00000360158.3	P08F94-1
	PKHD1	ENST00000340994.4	TSL:5	c.7733+33C>T		intron	N/A	ENSP00000341097.4	P08F94-2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61171 AN: 151898 Hom.: 13518 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.446 AC: 110795 AN: 248648 AF XY: 0.436

Gnomad AFR exome AF: 0.435

Gnomad AMR exome AF: 0.654

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.868

Gnomad FIN exome AF: 0.450

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.372

GnomAD4 exome AF: 0.355 AC: 512612 AN: 1445838 Hom.: 101390 Cov.: 29 AF XY: 0.358 AC XY: 257772 AN XY: 720194

African (AFR) AF: 0.419 AC: 13870 AN: 33106

American (AMR) AF: 0.634 AC: 28242 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 6526 AN: 25996

East Asian (EAS) AF: 0.828 AC: 32755 AN: 39576

South Asian (SAS) AF: 0.514 AC: 44084 AN: 85742

European-Finnish (FIN) AF: 0.436 AC: 23124 AN: 53070

Middle Eastern (MID) AF: 0.268 AC: 1541 AN: 5748

European-Non Finnish (NFE) AF: 0.310 AC: 340725 AN: 1098204

Other (OTH) AF: 0.363 AC: 21745 AN: 59844

GnomAD4 genome AF: 0.403 AC: 61210 AN: 152016 Hom.: 13527 Cov.: 33 AF XY: 0.418 AC XY: 31048 AN XY: 74312

African (AFR) AF: 0.432 AC: 17912 AN: 41474

American (AMR) AF: 0.532 AC: 8107 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3466

East Asian (EAS) AF: 0.852 AC: 4408 AN: 5176

South Asian (SAS) AF: 0.539 AC: 2599 AN: 4826

European-Finnish (FIN) AF: 0.453 AC: 4785 AN: 10566

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21534 AN: 67942

Other (OTH) AF: 0.366 AC: 774 AN: 2112

Alfa AF: 0.344 Hom.: 2029

Bravo AF: 0.407

Asia WGS AF: 0.622 AC: 2163 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Polycystic kidney disease 4 (2)
-	-	1	Autosomal recessive polycystic kidney disease (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.77
PhyloP100		-0.0060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9382044; hg19: chr6-51732628; COSMIC: COSV61899865;