Genetic Variant NM_138295.5:c.8130G>C (chr7-47800712-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138295.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PKD1L1	NM_138295.5	MANE Select	c.8130G>C	p.Gln2710His	missense	Exon 54 of 57	NP_612152.1	Q8TDX9-1
PKD1L1-AS1	NR_161268.1		n.153+5269C>G		intron	N/A
PKD1L1-AS1	NR_161269.1		n.153+5269C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PKD1L1	ENST00000289672.7	TSL:1 MANE Select	c.8130G>C	p.Gln2710His	missense	Exon 54 of 57	ENSP00000289672.2	Q8TDX9-1
PKD1L1-AS1	ENST00000623971.3	TSL:1	n.153+5269C>G		intron	N/A
PKD1L1	ENST00000690269.1		c.8130G>C	p.Gln2710His	missense	Exon 54 of 58	ENSP00000510743.1	A0A8I5KWV8

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

GnomAD2 exomes

AF:

0.0299

AC:

7511

AN:

251470

AF XY:

0.0318

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 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

African (AFR)

AF:

0.00272

AC:

AN:

33480

American (AMR)

AF:

0.0583

AC:

2609

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0568

AC:

1484

AN:

26136

East Asian (EAS)

AF:

0.000176

AC:

AN:

39700

South Asian (SAS)

AF:

0.0729

AC:

6286

AN:

86258

European-Finnish (FIN)

AF:

0.00719

AC:

384

AN:

53420

Middle Eastern (MID)

AF:

0.0309

AC:

178

AN:

5766

European-Non Finnish (NFE)

AF:

0.0189

AC:

20976

AN:

1111996

Other (OTH)

AF:

0.0241

AC:

1456

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

2118

4237

6355

8474

10592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0191

AC:

2908

AN:

152312

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1504

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00404

AC:

168

AN:

41562

American (AMR)

AF:

0.0438

AC:

670

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0579

AC:

201

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.0729

AC:

352

AN:

4826

European-Finnish (FIN)

AF:

0.00734

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0202

AC:

1372

AN:

68034

Other (OTH)

AF:

0.0232

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

152

303

455

606

758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

PKD1L1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.11

(source)

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

PhyloP100

-0.31

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over