Variant 7-47792779-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_138295.5(PKD1L1):c.8374T>C(p.Phe2792Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,572 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 13 hom. )

Consequence

PKD1L1
NM_138295.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.823

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:

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=0.0027688742).

BP6

Variant 7-47792779-A-G is Benign according to our data. Variant chr7-47792779-A-G is described in ClinVar as [Benign]. Clinvar id is 726413.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00106 (1551/1461294) while in subpopulation EAS AF= 0.0068 (270/39680). AF 95% confidence interval is 0.00614. There are 13 homozygotes in gnomad4_exome. There are 774 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L1	NM_138295.5 link	c.8374T>C	p.Phe2792Leu	missense_variant	56/57	ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3 link	c.8551T>C	p.Phe2851Leu	missense_variant	57/59		XP_016867287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672.7 link	c.8374T>C	p.Phe2792Leu	missense_variant	56/57	1	NM_138295.5	ENSP00000289672.2		Q8TDX9-1

Frequencies

GnomAD3 genomes

AF:

0.00181

AC:

276

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00578

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00262

AC:

656

AN:

250776

Hom.:

AF XY:

0.00250

AC XY:

339

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00702

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.000846

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00106

AC:

1551

AN:

1461294

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

774

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00680

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.0182

Gnomad4 NFE exome

AF:

0.000172

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.00181

AC:

275

AN:

152278

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00560

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0183

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000563

Hom.:

Bravo

AF:

0.000442

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00251

AC:

305

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 24, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.97

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.055

Sift

Benign

0.28

Sift4G

Benign

0.40

Polyphen

0.031

Vest4

0.26

MutPred

0.32

Gain of helix (P = 0.2294);

MVP

0.40

MPC

0.17

ClinPred

0.018

GERP RS

2.5

Varity_R

0.11

gMVP

0.20

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