5-131647075-A-G

Variant names:

• chr5-131647075-A-G
• rs26006
• NM_133372.3:c.3422+15T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.564

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]

ENSG00000273217 (HGNC:):

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNIP1	NM_133372.3	c.3422+15T>C		intron_variant	Intron 17 of 17	ENST00000510461.6	NP_588613.3
FNIP1	NM_001008738.3	c.3338+15T>C		intron_variant	Intron 16 of 16		NP_001008738.3
FNIP1	NM_001346114.2	c.3287+15T>C		intron_variant	Intron 16 of 16		NP_001333043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNIP1	ENST00000510461.6	c.3422+15T>C		intron_variant	Intron 17 of 17	1	NM_133372.3	ENSP00000421985.1
ENSG00000273217	ENST00000514667.1	c.220-42382T>C		intron_variant	Intron 2 of 28	2		ENSP00000426948.1
FNIP1	ENST00000307954.12	c.3287+15T>C		intron_variant	Intron 16 of 16	1		ENSP00000310453.8
FNIP1	ENST00000307968.11	c.3338+15T>C		intron_variant	Intron 16 of 16	5		ENSP00000309266.7

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97241 AN: 151886 Hom.: 33037 Cov.: 31

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

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.: 30 AF XY: 0.747 AC XY: 541841 AN XY: 725810

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.: 31 AF XY: 0.640 AC XY: 47514 AN XY: 74290

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

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Other links and lift over

dbSNP: rs26006; hg19: chr5-130982768; COSMIC: COSV57194743;