chr7-47953389-T-C

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L1	XM_017011798.3	c.-1029A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 59		XP_016867287.1
PKD1L1	XM_017011798.3	c.-1029A>G		5_prime_UTR_variant	Exon 1 of 59		XP_016867287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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 v4.3

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;