16-71931293-C-T

Variant names:

• chr16-71931293-C-T
• rs16973500
• NM_181536.2:c.4927-1110G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181536.2(PKD1L3):​c.4927-1110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,030 control chromosomes in the GnomAD database, including 1,771 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 0.14 (1771 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: PKD1L3 NM_181536.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

Genes affected

PKD1L3 (HGNC:21716): (polycystin 1 like 3, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded protein contains 11 transmembrane domains, a latrophilin/CL-1-like GPCR proteolytic site (GPS) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. This protein may function as a component of cation channel pores.[provided by RefSeq, Apr 2009]

IST1 (HGNC:28977): (IST1 factor associated with ESCRT-III) This gene encodes a protein with MIT-interacting motifs that interacts with components of endosomal sorting complexes required for transport (ESCRT). ESCRT functions in vesicle budding, such as that which occurs during membrane abscission in cytokinesis. There is a pseudogene for this gene on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L3	NM_181536.2	c.4927-1110G>A		intron_variant	Intron 28 of 29	ENST00000620267.2	NP_853514.1
IST1	NM_001270975.2	c.*3480C>T		downstream_gene_variant		ENST00000378799.11	NP_001257904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L3	ENST00000620267.2	c.4927-1110G>A		intron_variant	Intron 28 of 29	1	NM_181536.2	ENSP00000480090.1
IST1	ENST00000378799.11	c.*3480C>T		downstream_gene_variant		1	NM_001270975.2	ENSP00000368076.6

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20969 AN: 151888 Hom.: 1768 Cov.: 32

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.0417 AC: 1 AN: 24 Hom.: 0 AF XY: 0.0417 AC XY: 1 AN XY: 24

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0455

GnomAD4 genome AF: 0.138 AC: 20977 AN: 152006 Hom.: 1771 Cov.: 32 AF XY: 0.145 AC XY: 10771 AN XY: 74288

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.158

Alfa AF: 0.139 Hom.: 3093

Bravo AF: 0.127

Asia WGS AF: 0.312 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs16973500; hg19: chr16-71965196;