NM_133372.3:c.1202+8392C>T

Variant names:

• chr5-131690525-G-A
• rs152815
• NM_133372.3:c.1202+8392C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

FNIP1 Gene-Disease associations (from GenCC):

• FNIP1-associated syndrome

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• immunodeficiency 93 and hypertrophic cardiomyopathy

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000273217 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FNIP1	NM_133372.3	c.1202+8392C>T		intron_variant	Intron 11 of 17	ENST00000510461.6	NP_588613.3
FNIP1	NM_001008738.3	c.1118+8392C>T		intron_variant	Intron 10 of 16		NP_001008738.3
FNIP1	NM_001346114.2	c.1067+8392C>T		intron_variant	Intron 10 of 16		NP_001333043.1
FNIP1	NM_001346113.2	c.1202+8392C>T		intron_variant	Intron 11 of 12		NP_001333042.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNIP1	ENST00000510461.6	c.1202+8392C>T		intron_variant	Intron 11 of 17	1	NM_133372.3	ENSP00000421985.1
ENSG00000273217	ENST00000514667.1	c.219+54039C>T		intron_variant	Intron 2 of 28	2		ENSP00000426948.1

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

African (AFR) AF: 0.0700 AC: 2898 AN: 41426

American (AMR) AF: 0.258 AC: 3939 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3466

East Asian (EAS) AF: 0.00272 AC: 14 AN: 5152

South Asian (SAS) AF: 0.0943 AC: 455 AN: 4824

European-Finnish (FIN) AF: 0.267 AC: 2820 AN: 10550

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25335 AN: 67902

Other (OTH) AF: 0.278 AC: 585 AN: 2104

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
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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