5-131774432-C-A

Position:

• chr5-131774432-C-A

Variant summary

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

The NM_133372.3(FNIP1):​c.92+22398G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,164 control chromosomes in the GnomAD database, including 29,760 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 0.58 (29760 hom., cov: 33)
• Consequence: FNIP1 NM_133372.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNIP1	NM_133372.3	c.92+22398G>T		intron_variant		ENST00000510461.6
FNIP1	NM_001008738.3	c.92+22398G>T		intron_variant
FNIP1	NM_001346113.2	c.92+22398G>T		intron_variant
FNIP1	NM_001346114.2	c.92+22398G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNIP1	ENST00000510461.6	c.92+22398G>T		intron_variant		1	NM_133372.3	P4
FNIP1	ENST00000307954.12	c.92+22398G>T		intron_variant		1
FNIP1	ENST00000511848.1	c.92+22398G>T		intron_variant		1
FNIP1	ENST00000307968.11	c.92+22398G>T		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87728 AN: 152046 Hom.: 29762 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.577 AC: 87734 AN: 152164 Hom.: 29760 Cov.: 33 AF XY: 0.579 AC XY: 43052 AN XY: 74398

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.626

Alfa AF: 0.633 Hom.: 5222

Bravo AF: 0.552

Asia WGS AF: 0.571 AC: 1984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0070
DANN	Benign	0.37

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: rs6870930; hg19: chr5-131110125;