Genetic Variant NM_133372.3:c.92+22398G>T (chr5-131774432-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.04

Publications

2 publications found

Variant links:

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)

FNIP1 links:

ENSG00000273217 (HGNC:):

ENSG00000273217 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
FNIP1	NM_133372.3 link	c.92+22398G>T	intron_variant	Intron 1 of 17	ENST00000510461.6	NP_588613.3
FNIP1	NM_001008738.3 link	c.92+22398G>T	intron_variant	Intron 1 of 16		NP_001008738.3
FNIP1	NM_001346114.2 link	c.92+22398G>T	intron_variant	Intron 1 of 16		NP_001333043.1
FNIP1	NM_001346113.2 link	c.92+22398G>T	intron_variant	Intron 1 of 12		NP_001333042.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNIP1	ENST00000510461.6 link	c.92+22398G>T		intron_variant	Intron 1 of 17	1	NM_133372.3	ENSP00000421985.1
ENSG00000273217	ENST00000514667.1 link	c.92+22398G>T		intron_variant	Intron 1 of 28	2		ENSP00000426948.1

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87728

AN:

152046

Hom.:

29762

Cov.:

show subpopulations

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.:

AF XY:

0.579

AC XY:

43052

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.194

AC:

8037

AN:

41508

American (AMR)

AF:

0.652

AC:

9962

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.627

AC:

2177

AN:

3470

East Asian (EAS)

AF:

0.507

AC:

2627

AN:

5184

South Asian (SAS)

AF:

0.695

AC:

3355

AN:

4824

European-Finnish (FIN)

AF:

0.704

AC:

7449

AN:

10584

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.764

AC:

51941

AN:

67996

Other (OTH)

AF:

0.626

AC:

1321

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1479

2958

4438

5917

7396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.670

Hom.:

54021

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

(source)

DANN

Benign

0.37

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over