rs6955251

Positions:

• chr7-47933437-G-A
• chr7-47933437-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138295.5(PKD1L1):​c.399-1381C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,944 control chromosomes in the GnomAD database, including 4,151 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 0.23 (4151 hom., cov: 32)
• Consequence: PKD1L1 NM_138295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L1	NM_138295.5	c.399-1381C>T		intron_variant		ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3	c.576-1381C>T		intron_variant			XP_016867287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672.7	c.399-1381C>T		intron_variant		1	NM_138295.5	ENSP00000289672	P2
PKD1L1	ENST00000685709.1	c.399-1381C>T		intron_variant				ENSP00000509540	A2
PKD1L1	ENST00000690269.1	c.399-1381C>T		intron_variant				ENSP00000510743	A2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34215 AN: 151824 Hom.: 4136 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.226 AC: 34282 AN: 151944 Hom.: 4151 Cov.: 32 AF XY: 0.227 AC XY: 16842 AN XY: 74278

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.226

Alfa AF: 0.215 Hom.: 5177

Bravo AF: 0.230

Asia WGS AF: 0.352 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs6955251; hg19: chr7-47973034;