Genetic Variant PKD1L1:c.8194-66C>T (chr7-47796216-G-A) – 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.8194-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,326,426 control chromosomes in the GnomAD database, including 157,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.44 ( 15403 hom., cov: 33)

Exomes 𝑓: 0.49 ( 142192 hom. )

Consequence

PKD1L1
NM_138295.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.731

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 7-47796216-G-A is Benign according to our data. Variant chr7-47796216-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276259.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 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	Effect	Exon Rank	Protein	UniProt
PKD1L1	NM_138295.5	MANE Select	c.8194-66C>T	intron	N/A	NP_612152.1	Q8TDX9-1
PKD1L1-AS1	NR_161268.1		n.153+773G>A	intron	N/A
PKD1L1-AS1	NR_161269.1		n.153+773G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PKD1L1	ENST00000289672.7	TSL:1 MANE Select	c.8194-66C>T	intron	N/A	ENSP00000289672.2	Q8TDX9-1
PKD1L1-AS1	ENST00000623971.3	TSL:1	n.153+773G>A	intron	N/A
PKD1L1	ENST00000690269.1		c.8194-66C>T	intron	N/A	ENSP00000510743.1	A0A8I5KWV8

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

66936

AN:

151854

Hom.:

15399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.595

Gnomad SAS

AF:

0.434

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.496

Gnomad OTH

AF:

0.474

GnomAD4 exome

AF:

0.490

AC:

575927

AN:

1174454

Hom.:

142192

AF XY:

0.490

AC XY:

287889

AN XY:

587984

show subpopulations

African (AFR)

AF:

0.300

AC:

7852

AN:

26138

American (AMR)

AF:

0.476

AC:

12651

AN:

26602

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

9273

AN:

20204

East Asian (EAS)

AF:

0.590

AC:

22319

AN:

37804

South Asian (SAS)

AF:

0.434

AC:

28602

AN:

65868

European-Finnish (FIN)

AF:

0.412

AC:

17503

AN:

42468

Middle Eastern (MID)

AF:

0.484

AC:

1806

AN:

3734

European-Non Finnish (NFE)

AF:

0.501

AC:

451669

AN:

901332

Other (OTH)

AF:

0.482

AC:

24252

AN:

50304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

13889

27777

41666

55554

69443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12638

25276

37914

50552

63190

<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:

0.440

AC:

66943

AN:

151972

Hom.:

15403

Cov.:

AF XY:

0.438

AC XY:

32515

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.312

AC:

12947

AN:

41450

American (AMR)

AF:

0.506

AC:

7738

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

1602

AN:

3468

East Asian (EAS)

AF:

0.595

AC:

3071

AN:

5162

South Asian (SAS)

AF:

0.434

AC:

2090

AN:

4814

European-Finnish (FIN)

AF:

0.409

AC:

4304

AN:

10514

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.496

AC:

33708

AN:

67960

Other (OTH)

AF:

0.478

AC:

1009

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1894

3788

5683

7577

9471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.456

Hom.:

3167

Bravo

AF:

0.440

Asia WGS

AF:

0.492

AC:

1709

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.46

(source)

DANN

Benign

0.66

PhyloP100

-0.73

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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