rs2686821

Variant names:

• chr7-47935485-G-A
• rs2686821
• NM_138295.5:c.398+1361C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138295.5(PKD1L1):​c.398+1361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,104 control chromosomes in the GnomAD database, including 20,291 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 0.52 (20291 hom., cov: 33)
• Consequence: PKD1L1 NM_138295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 8, autosomal

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L1	NM_138295.5	c.398+1361C>T		intron_variant	Intron 4 of 56	ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3	c.575+1361C>T		intron_variant	Intron 5 of 58		XP_016867287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672.7	c.398+1361C>T		intron_variant	Intron 4 of 56	1	NM_138295.5	ENSP00000289672.2
PKD1L1	ENST00000690269.1	c.398+1361C>T		intron_variant	Intron 4 of 57			ENSP00000510743.1
PKD1L1	ENST00000685709.1	c.398+1361C>T		intron_variant	Intron 4 of 55			ENSP00000509540.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78398 AN: 151986 Hom.: 20276 Cov.: 33

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.488

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.516 AC: 78443 AN: 152104 Hom.: 20291 Cov.: 33 AF XY: 0.520 AC XY: 38692 AN XY: 74378

African (AFR) AF: 0.515 AC: 21357 AN: 41476

American (AMR) AF: 0.530 AC: 8111 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1556 AN: 3472

East Asian (EAS) AF: 0.530 AC: 2748 AN: 5186

South Asian (SAS) AF: 0.398 AC: 1919 AN: 4820

European-Finnish (FIN) AF: 0.581 AC: 6137 AN: 10560

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35052 AN: 67980

Other (OTH) AF: 0.486 AC: 1025 AN: 2110

Alfa AF: 0.508 Hom.: 62957

Bravo AF: 0.510

Asia WGS AF: 0.478 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.20
DANN	Benign	0.69
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2686821; hg19: chr7-47975082;