rs26006

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-131647075-A-G
• chr5-131647075-A-C
• chr5-131647075-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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: DEFINITIVE 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133372.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNIP1	NM_133372.3	MANE Select	c.3422+15T>C		intron	N/A	NP_588613.3	Q8TF40-1
	FNIP1	NM_001008738.3		c.3338+15T>C		intron	N/A	NP_001008738.3	Q8TF40-3
	FNIP1	NM_001346114.2		c.3287+15T>C		intron	N/A	NP_001333043.1	J3KNG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNIP1	ENST00000510461.6	TSL:1 MANE Select	c.3422+15T>C		intron	N/A	ENSP00000421985.1	Q8TF40-1
	ENSG00000273217	ENST00000514667.1	TSL:2	c.220-42382T>C		intron	N/A	ENSP00000426948.1	E9PCH4
	FNIP1	ENST00000307954.12	TSL:1	c.3287+15T>C		intron	N/A	ENSP00000310453.8	J3KNG8

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

GnomAD2 exomes AF: 0.692 AC: 173057 AN: 250062 AF XY: 0.707

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 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

African (AFR) AF: 0.369 AC: 12329 AN: 33382

American (AMR) AF: 0.635 AC: 28214 AN: 44444

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 16950 AN: 26072

East Asian (EAS) AF: 0.504 AC: 19994 AN: 39652

South Asian (SAS) AF: 0.742 AC: 63818 AN: 86014

European-Finnish (FIN) AF: 0.698 AC: 37257 AN: 53384

Middle Eastern (MID) AF: 0.700 AC: 4028 AN: 5756

European-Non Finnish (NFE) AF: 0.776 AC: 861345 AN: 1109806

Other (OTH) AF: 0.715 AC: 43111 AN: 60270

GnomAD4 genome AF: 0.640 AC: 97259 AN: 152004 Hom.: 33039 Cov.: 31 AF XY: 0.640 AC XY: 47514 AN XY: 74290

African (AFR) AF: 0.390 AC: 16165 AN: 41408

American (AMR) AF: 0.685 AC: 10454 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2276 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2623 AN: 5162

South Asian (SAS) AF: 0.730 AC: 3517 AN: 4818

European-Finnish (FIN) AF: 0.705 AC: 7454 AN: 10568

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.772 AC: 52463 AN: 67998

Other (OTH) AF: 0.680 AC: 1434 AN: 2110

Alfa AF: 0.698 Hom.: 10909

Bravo AF: 0.624

Asia WGS AF: 0.598 AC: 2078 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.65
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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