5-131744115-C-T

Variant names:

• chr5-131744115-C-T
• rs13164236
• NM_133372.3:c.219+449G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133372.3(FNIP1):​c.219+449G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 151,630 control chromosomes in the GnomAD database, including 46,990 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 0.79 (46990 hom., cov: 28)
• Consequence: FNIP1 NM_133372.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNIP1	NM_133372.3	c.219+449G>A		intron_variant	Intron 2 of 17	ENST00000510461.6	NP_588613.3
FNIP1	NM_001008738.3	c.219+449G>A		intron_variant	Intron 2 of 16		NP_001008738.3
FNIP1	NM_001346114.2	c.219+449G>A		intron_variant	Intron 2 of 16		NP_001333043.1
FNIP1	NM_001346113.2	c.219+449G>A		intron_variant	Intron 2 of 12		NP_001333042.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNIP1	ENST00000510461.6	c.219+449G>A		intron_variant	Intron 2 of 17	1	NM_133372.3	ENSP00000421985.1
ENSG00000273217	ENST00000514667.1	c.219+449G>A		intron_variant	Intron 2 of 28	2		ENSP00000426948.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119014 AN: 151512 Hom.: 46958 Cov.: 28

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.785 AC: 119099 AN: 151630 Hom.: 46990 Cov.: 28 AF XY: 0.780 AC XY: 57776 AN XY: 74084

African (AFR) AF: 0.831 AC: 34311 AN: 41308

American (AMR) AF: 0.752 AC: 11454 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2500 AN: 3466

East Asian (EAS) AF: 0.509 AC: 2617 AN: 5138

South Asian (SAS) AF: 0.754 AC: 3619 AN: 4802

European-Finnish (FIN) AF: 0.715 AC: 7469 AN: 10446

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54553 AN: 67930

Other (OTH) AF: 0.794 AC: 1666 AN: 2098

Alfa AF: 0.780 Hom.: 5639

Bravo AF: 0.788

Asia WGS AF: 0.636 AC: 2209 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.065
DANN	Benign	0.44
PhyloP100		-3.1
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: rs13164236; hg19: chr5-131079808;