Variant chr5-131647075-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_133372.3(FNIP1):c.3422+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 1,610,784 control chromosomes in the GnomAD database, including 443,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 33039 hom., cov: 31)

Exomes 𝑓: 0.75 ( 410245 hom. )

Consequence

FNIP1
NM_133372.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.564

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 links:

ENSG00000273217 (HGNC:):

ENSG00000273217 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-131647075-A-G is Benign according to our data. Variant chr5-131647075-A-G is described in ClinVar as [Benign]. Clinvar id is 2413988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
FNIP1	NM_133372.3 linkuse as main transcript	c.3422+15T>C	intron_variant	ENST00000510461.6	NP_588613.3	Q8TF40-1
FNIP1	NM_001008738.3 linkuse as main transcript	c.3338+15T>C	intron_variant		NP_001008738.3	Q8TF40-3
FNIP1	NM_001346114.2 linkuse as main transcript	c.3287+15T>C	intron_variant		NP_001333043.1	J3KNG8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FNIP1	ENST00000510461.6 linkuse as main transcript	c.3422+15T>C	intron_variant	1	NM_133372.3	ENSP00000421985.1	Q8TF40-1
ENSG00000273217	ENST00000514667.1 linkuse as main transcript	c.220-42382T>C	intron_variant	2		ENSP00000426948.1	E9PCH4
FNIP1	ENST00000307954.12 linkuse as main transcript	c.3287+15T>C	intron_variant	1		ENSP00000310453.8	J3KNG8
FNIP1	ENST00000307968.11 linkuse as main transcript	c.3338+15T>C	intron_variant	5		ENSP00000309266.7	Q8TF40-3

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

97241

AN:

151886

Hom.:

33037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.731

Gnomad AMR

AF:

0.685

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.730

Gnomad FIN

AF:

0.705

Gnomad MID

AF:

0.713

Gnomad NFE

AF:

0.772

Gnomad OTH

AF:

0.679

GnomAD3 exomes

AF:

0.692

AC:

173057

AN:

250062

Hom.:

61515

AF XY:

0.707

AC XY:

95490

AN XY:

135096

show subpopulations

Gnomad AFR exome

AF:

0.383

Gnomad AMR exome

AF:

0.628

Gnomad ASJ exome

AF:

0.646

Gnomad EAS exome

AF:

0.519

Gnomad SAS exome

AF:

0.742

Gnomad FIN exome

AF:

0.695

Gnomad NFE exome

AF:

0.772

Gnomad OTH exome

AF:

0.716

GnomAD4 exome

AF:

0.745

AC:

1087046

AN:

1458780

Hom.:

410245

Cov.:

AF XY:

0.747

AC XY:

541841

AN XY:

725810

show subpopulations

Gnomad4 AFR exome

AF:

0.369

Gnomad4 AMR exome

AF:

0.635

Gnomad4 ASJ exome

AF:

0.650

Gnomad4 EAS exome

AF:

0.504

Gnomad4 SAS exome

AF:

0.742

Gnomad4 FIN exome

AF:

0.698

Gnomad4 NFE exome

AF:

0.776

Gnomad4 OTH exome

AF:

0.715

GnomAD4 genome

AF:

0.640

AC:

97259

AN:

152004

Hom.:

33039

Cov.:

AF XY:

0.640

AC XY:

47514

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.685

Gnomad4 ASJ

AF:

0.656

Gnomad4 EAS

AF:

0.508

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.705

Gnomad4 NFE

AF:

0.772

Gnomad4 OTH

AF:

0.680

Alfa

AF:

0.704

Hom.:

10847

Bravo

AF:

0.624

Asia WGS

AF:

0.598

AC:

2078

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 89% of patients studied by a panel of primary immunodeficiencies. Number of patients: 85. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.1

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over