7-47789719-T-C

Variant names:

• chr7-47789719-T-C
• rs1551277
• NM_138295.5:c.8526+2908A>G

Variant summary

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

The NM_138295.5(PKD1L1):​c.8526+2908A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,006 control chromosomes in the GnomAD database, including 37,608 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 0.70 (37608 hom., cov: 32)
• Consequence: PKD1L1 NM_138295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L1	NM_138295.5	c.8526+2908A>G		intron_variant	Intron 56 of 56	ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3	c.8704-2347A>G		intron_variant	Intron 57 of 58		XP_016867287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672.7	c.8526+2908A>G		intron_variant	Intron 56 of 56	1	NM_138295.5	ENSP00000289672.2
PKD1L1	ENST00000690269.1	c.8527-2347A>G		intron_variant	Intron 56 of 57			ENSP00000510743.1
PKD1L1	ENST00000685709.1	c.8358+2908A>G		intron_variant	Intron 55 of 55			ENSP00000509540.1
PKD1L1	ENST00000648482.1	c.1158+2908A>G		intron_variant	Intron 7 of 7			ENSP00000496786.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106525 AN: 151888 Hom.: 37576 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.701 AC: 106603 AN: 152006 Hom.: 37608 Cov.: 32 AF XY: 0.703 AC XY: 52182 AN XY: 74272

African (AFR) AF: 0.656 AC: 27172 AN: 41450

American (AMR) AF: 0.702 AC: 10721 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2597 AN: 3472

East Asian (EAS) AF: 0.639 AC: 3304 AN: 5174

South Asian (SAS) AF: 0.632 AC: 3037 AN: 4808

European-Finnish (FIN) AF: 0.749 AC: 7882 AN: 10522

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49505 AN: 67986

Other (OTH) AF: 0.710 AC: 1500 AN: 2114

Alfa AF: 0.710 Hom.: 19259

Bravo AF: 0.695

Asia WGS AF: 0.634 AC: 2207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.073
DANN	Benign	0.79
PhyloP100		-1.5
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: rs1551277; hg19: chr7-47829317;