XM_017011798.3:c.-1029A>G

Variant names:

• chr7-47953389-T-C
• rs2686831
• XM_017011798.3:c.-1029A>G

Variant summary

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

The XM_017011798.3(PKD1L1):​c.-1029A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,002 control chromosomes in the GnomAD database, including 16,795 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 0.46 (16795 hom., cov: 32)
• Consequence: PKD1L1 XM_017011798.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

 

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
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69844 AN: 151884 Hom.: 16798 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.460 AC: 69860 AN: 152002 Hom.: 16795 Cov.: 32 AF XY: 0.465 AC XY: 34520 AN XY: 74286

African (AFR) AF: 0.314 AC: 13036 AN: 41462

American (AMR) AF: 0.497 AC: 7587 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1564 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2760 AN: 5164

South Asian (SAS) AF: 0.388 AC: 1864 AN: 4804

European-Finnish (FIN) AF: 0.591 AC: 6236 AN: 10556

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35319 AN: 67958

Other (OTH) AF: 0.448 AC: 947 AN: 2114

Alfa AF: 0.498 Hom.: 9117

Bravo AF: 0.446

Asia WGS AF: 0.476 AC: 1657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.015
DANN	Benign	0.24
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs2686831; hg19: chr7-47992986;