rs152815

chr5-131690525-G-Achr5-131690525-G-C

Variant summary

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

The NM_133372.3(FNIP1):c.1202+8392C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,882 control chromosomes in the GnomAD database, including 6,068 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 0.25 (6068 hom., cov: 31)
• Consequence: FNIP1 NM_133372.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

Genes affected

FNIP1 (HGNC:29418): (folliculin interacting protein 1) This gene encodes a protein that binds to the tumor suppressor protein folliculin and to AMP-activated protein kinase (AMPK). The encoded protein participates in the regulation of cellular metabolism and nutrient sensing by modulating the AMPK and target of rapamycin signaling pathways. This gene has a closely related paralog that encodes a protein with similar binding activities. Both related proteins also associate with the molecular chaperone heat shock protein-90 (Hsp90) and negatively regulate its ATPase activity and facilitate its association with folliculin. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNIP1	NM_133372.3	c.1202+8392C>T		intron_variant		ENST00000510461.6
FNIP1	NM_001008738.3	c.1118+8392C>T		intron_variant
FNIP1	NM_001346113.2	c.1202+8392C>T		intron_variant
FNIP1	NM_001346114.2	c.1067+8392C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNIP1	ENST00000510461.6	c.1202+8392C>T		intron_variant		1	NM_133372.3	P4
FNIP1	ENST00000307954.12	c.1067+8392C>T		intron_variant		1
FNIP1	ENST00000511848.1	c.1202+8392C>T		intron_variant		1
FNIP1	ENST00000307968.11	c.1118+8392C>T		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37393 AN: 151764 Hom.: 6070 Cov.: 31

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.246 AC: 37384 AN: 151882 Hom.: 6068 Cov.: 31 AF XY: 0.236 AC XY: 17489 AN XY: 74248

Gnomad4 AFR AF: 0.0700

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.00272

Gnomad4 SAS AF: 0.0943

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.278

Alfa AF: 0.284 Hom.: 838

Bravo AF: 0.242

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.5
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs152815; hg19: chr5-131026218; COSMIC: COSV57194831;