NM_138295.5:c.8527-165A>G

Variant names:

• chr7-47775331-T-C
• rs6949512
• NM_138295.5:c.8527-165A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138295.5(PKD1L1):​c.8527-165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 152,284 control chromosomes in the GnomAD database, including 843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.092 (843 hom., cov: 33)
• Consequence: PKD1L1 NM_138295.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.458

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-47775331-T-C is Benign according to our data. Variant chr7-47775331-T-C is described in ClinVar as [Benign]. Clinvar id is 1233358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L1	NM_138295.5	c.8527-165A>G		intron_variant	Intron 56 of 56	ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3	c.8740-165A>G		intron_variant	Intron 58 of 58		XP_016867287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672.7	c.8527-165A>G		intron_variant	Intron 56 of 56	1	NM_138295.5	ENSP00000289672.2
PKD1L1	ENST00000690269.1	c.8563-165A>G		intron_variant	Intron 57 of 57			ENSP00000510743.1
PKD1L1	ENST00000685709.1	c.8359-165A>G		intron_variant	Intron 55 of 55			ENSP00000509540.1
PKD1L1	ENST00000648482.1	c.1158+17296A>G		intron_variant	Intron 7 of 7			ENSP00000496786.1

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13981 AN: 152164 Hom.: 836 Cov.: 33

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0884

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

GnomAD4 genome AF: 0.0919 AC: 14000 AN: 152284 Hom.: 843 Cov.: 33 AF XY: 0.0916 AC XY: 6824 AN XY: 74470

Gnomad4 AFR AF: 0.0381

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0853

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0899

Alfa AF: 0.0760 Hom.: 171

Bravo AF: 0.0959

Asia WGS AF: 0.166 AC: 578 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.71

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: rs6949512; hg19: chr7-47814929;