rs921630

Variant names:

• chr7-47755460-A-G
• rs921630
• ENST00000648482.1:c.1159-14547T>C

Variant summary

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

The ENST00000648482.1(PKD1L1):​c.1159-14547T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,972 control chromosomes in the GnomAD database, including 17,035 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 0.47 (17035 hom., cov: 32)
• Consequence: PKD1L1 ENST00000648482.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• 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, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648482.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L1	ENST00000648482.1		c.1159-14547T>C		intron	N/A	ENSP00000496786.1	A0A3B3IRH7

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71196 AN: 151854 Hom.: 17022 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.469 AC: 71247 AN: 151972 Hom.: 17035 Cov.: 32 AF XY: 0.471 AC XY: 35000 AN XY: 74280

African (AFR) AF: 0.412 AC: 17073 AN: 41442

American (AMR) AF: 0.544 AC: 8314 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1482 AN: 3468

East Asian (EAS) AF: 0.598 AC: 3087 AN: 5164

South Asian (SAS) AF: 0.443 AC: 2135 AN: 4824

European-Finnish (FIN) AF: 0.490 AC: 5155 AN: 10524

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32402 AN: 67944

Other (OTH) AF: 0.474 AC: 1001 AN: 2110

Alfa AF: 0.472 Hom.: 47891

Bravo AF: 0.471

Asia WGS AF: 0.522 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.82
PhyloP100		0.30

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs921630;

hg19: chr7-47795058;