rs9395699

Variant names:

• chr6-51619550-G-A
• rs9395699
• NM_138694.4:c.11786-30C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-51619550-G-A
• chr6-51619550-G-T

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.11786-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,575,624 control chromosomes in the GnomAD database, including 24,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1908 hom., cov: 33)
  • Exomes 𝑓: 0.17 (22362 hom.)
• Consequence: PKHD1 NM_138694.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0380
• Publications: 5 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

ENSG00000228689 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-51619550-G-A is Benign according to our data. Variant chr6-51619550-G-A is described in ClinVar as Benign. ClinVar VariationId is 262386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 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.11786-30C>T		intron	N/A	NP_619639.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKHD1	ENST00000371117.8	TSL:1 MANE Select	c.11786-30C>T		intron	N/A	ENSP00000360158.3	P08F94-1
	ENSG00000228689	ENST00000454361.1	TSL:3	n.81-2805G>A		intron	N/A
	ENSG00000228689	ENST00000589278.6	TSL:5	n.811-2810G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22195 AN: 152016 Hom.: 1908 Cov.: 33

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.135

GnomAD2 exomes AF: 0.176 AC: 43306 AN: 246564 AF XY: 0.179

Gnomad AFR exome AF: 0.0783

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.390

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.173 AC: 245822 AN: 1423490 Hom.: 22362 Cov.: 25 AF XY: 0.174 AC XY: 123577 AN XY: 710710

African (AFR) AF: 0.0715 AC: 2344 AN: 32770

American (AMR) AF: 0.105 AC: 4682 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 4068 AN: 25876

East Asian (EAS) AF: 0.324 AC: 12782 AN: 39480

South Asian (SAS) AF: 0.200 AC: 17067 AN: 85268

European-Finnish (FIN) AF: 0.178 AC: 9383 AN: 52834

Middle Eastern (MID) AF: 0.135 AC: 773 AN: 5712

European-Non Finnish (NFE) AF: 0.172 AC: 184985 AN: 1077902

Other (OTH) AF: 0.165 AC: 9738 AN: 59008

GnomAD4 genome AF: 0.146 AC: 22199 AN: 152134 Hom.: 1908 Cov.: 33 AF XY: 0.149 AC XY: 11073 AN XY: 74356

African (AFR) AF: 0.0762 AC: 3162 AN: 41514

American (AMR) AF: 0.117 AC: 1788 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3464

East Asian (EAS) AF: 0.358 AC: 1852 AN: 5178

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4820

European-Finnish (FIN) AF: 0.182 AC: 1923 AN: 10578

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.167 AC: 11371 AN: 67972

Other (OTH) AF: 0.135 AC: 285 AN: 2110

Alfa AF: 0.157 Hom.: 6874

Bravo AF: 0.141

Asia WGS AF: 0.238 AC: 826 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.26
PhyloP100		0.038
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: rs9395699; hg19: chr6-51484348; COSMIC: COSV64401020; COSMIC: COSV64401020;