rs4724620

Variant names:

• chr7-47751314-T-C
• rs4724620
• ENST00000648482.1:c.1159-10401A>G

Variant summary

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

The ENST00000648482.1(PKD1L1):​c.1159-10401A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,090 control chromosomes in the GnomAD database, including 59,430 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 0.88 (59430 hom., cov: 30)
• Consequence: PKD1L1 ENST00000648482.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000648482.1	c.1159-10401A>G		intron_variant	Intron 7 of 7			ENSP00000496786.1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134214 AN: 151972 Hom.: 59379 Cov.: 30

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.883 AC: 134322 AN: 152090 Hom.: 59430 Cov.: 30 AF XY: 0.887 AC XY: 65939 AN XY: 74312

African (AFR) AF: 0.891 AC: 36959 AN: 41484

American (AMR) AF: 0.891 AC: 13612 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2786 AN: 3470

East Asian (EAS) AF: 0.978 AC: 5018 AN: 5132

South Asian (SAS) AF: 0.854 AC: 4099 AN: 4802

European-Finnish (FIN) AF: 0.910 AC: 9644 AN: 10594

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59265 AN: 68008

Other (OTH) AF: 0.876 AC: 1852 AN: 2114

Alfa AF: 0.874 Hom.: 111879

Bravo AF: 0.883

Asia WGS AF: 0.932 AC: 3241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
DANN	Benign	0.58
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4724620; hg19: chr7-47790912;