Genetic Variant PKD1L3:c.4927-1110G>A (chr16-71931293-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181536.2(PKD1L3):c.4927-1110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,030 control chromosomes in the GnomAD database, including 1,771 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1771 hom., cov: 32)

Exomes 𝑓: 0.042 ( 0 hom. )

Consequence

PKD1L3
NM_181536.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.270

Publications

22 publications found

Variant links:

Genes affected

PKD1L3 (HGNC:21716): (polycystin 1 like 3, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded protein contains 11 transmembrane domains, a latrophilin/CL-1-like GPCR proteolytic site (GPS) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. This protein may function as a component of cation channel pores.[provided by RefSeq, Apr 2009]

PKD1L3 links:

IST1 (HGNC:28977): (IST1 factor associated with ESCRT-III) This gene encodes a protein with MIT-interacting motifs that interacts with components of endosomal sorting complexes required for transport (ESCRT). ESCRT functions in vesicle budding, such as that which occurs during membrane abscission in cytokinesis. There is a pseudogene for this gene on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

IST1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L3	NM_181536.2 link	c.4927-1110G>A		intron_variant	Intron 28 of 29	ENST00000620267.2	NP_853514.1
IST1	NM_001270975.2 link	c.*3480C>T		downstream_gene_variant		ENST00000378799.11	NP_001257904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L3	ENST00000620267.2 link	c.4927-1110G>A		intron_variant	Intron 28 of 29	1	NM_181536.2	ENSP00000480090.1
IST1	ENST00000378799.11 link	c.*3480C>T		downstream_gene_variant		1	NM_001270975.2	ENSP00000368076.6

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20969

AN:

151888

Hom.:

1768

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0788

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.383

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.154

GnomAD4 exome

AF:

0.0417

AC:

AN:

Hom.:

AF XY:

0.0417

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0455

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.138

AC:

20977

AN:

152006

Hom.:

1771

Cov.:

AF XY:

0.145

AC XY:

10771

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.0786

AC:

3259

AN:

41440

American (AMR)

AF:

0.140

AC:

2137

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

597

AN:

3466

East Asian (EAS)

AF:

0.259

AC:

1337

AN:

5170

South Asian (SAS)

AF:

0.382

AC:

1839

AN:

4816

European-Finnish (FIN)

AF:

0.199

AC:

2098

AN:

10562

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9163

AN:

67966

Other (OTH)

AF:

0.158

AC:

333

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

887

1773

2660

3546

4433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<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:

0.137

Hom.:

6438

Bravo

AF:

0.127

Asia WGS

AF:

0.312

AC:

1085

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.6

(source)

DANN

Benign

0.71

PhyloP100

-0.27

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over