7-47800712-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_138295.5(PKD1L1):c.8130G>C(p.Gln2710His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,614,188 control chromosomes in the GnomAD database, including 693 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 47 hom., cov: 32)

Exomes 𝑓: 0.023 ( 646 hom. )

Consequence

PKD1L1
NM_138295.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.307

Variant links:

Genes affected

PKD1L1 (HGNC:18053): (polycystin 1 like 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family containing 11 transmembrane domains, a receptor for egg jelly (REJ) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. The encoded protein may play a role in the male reproductive system. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

PKD1L1 links:

PKD1L1-AS1 (HGNC:21911): (PKD1L1 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PKD1L1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022588074).

BP6

Variant 7-47800712-C-G is Benign according to our data. Variant chr7-47800712-C-G is described in ClinVar as [Benign]. Clinvar id is 2027216.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PKD1L1	NM_138295.5 link	c.8130G>C	p.Gln2710His	missense_variant	Exon 54 of 57	ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3 link	c.8307G>C	p.Gln2769His	missense_variant	Exon 55 of 59		XP_016867287.1
PKD1L1-AS1	NR_161268.1 link	n.153+5269C>G		intron_variant	Intron 1 of 2
PKD1L1-AS1	NR_161269.1 link	n.153+5269C>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672.7 link	c.8130G>C	p.Gln2710His	missense_variant	Exon 54 of 57	1	NM_138295.5	ENSP00000289672.2		Q8TDX9-1

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2898

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00405

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0434

Gnomad ASJ

AF:

0.0579

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0720

Gnomad FIN

AF:

0.00734

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.0299

AC:

7511

AN:

251470

Hom.:

194

AF XY:

0.0318

AC XY:

4326

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00338

Gnomad AMR exome

AF:

0.0568

Gnomad ASJ exome

AF:

0.0606

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0703

Gnomad FIN exome

AF:

0.00744

Gnomad NFE exome

AF:

0.0210

Gnomad OTH exome

AF:

0.0274

GnomAD4 exome

AF:

0.0229

AC:

33471

AN:

1461876

Hom.:

646

Cov.:

AF XY:

0.0245

AC XY:

17840

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.0583

Gnomad4 ASJ exome

AF:

0.0568

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0729

Gnomad4 FIN exome

AF:

0.00719

Gnomad4 NFE exome

AF:

0.0189

Gnomad4 OTH exome

AF:

0.0241

GnomAD4 genome

AF:

0.0191

AC:

2908

AN:

152312

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1504

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00404

Gnomad4 AMR

AF:

0.0438

Gnomad4 ASJ

AF:

0.0579

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0729

Gnomad4 FIN

AF:

0.00734

Gnomad4 NFE

AF:

0.0202

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0229

Hom.:

Bravo

AF:

0.0203

TwinsUK

AF:

0.0170

AC:

ALSPAC

AF:

0.0156

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0209

AC:

180

ExAC

AF:

0.0291

AC:

3536

Asia WGS

AF:

0.0290

AC:

AN:

3478

EpiCase

AF:

0.0228

EpiControl

AF:

0.0222

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PKD1L1-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.11

DANN

Benign

0.34

DEOGEN2

Benign

0.018

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.20

REVEL

Benign

0.066

Sift

Benign

0.56

Sift4G

Benign

0.62

Polyphen

0.0020

Vest4

0.045

MutPred

0.52

Loss of ubiquitination at K2707 (P = 0.1099);

MPC

0.088

ClinPred

0.00071

GERP RS

0.51

Varity_R

0.028

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over