Variant 17-82091249-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004104.5(FASN):c.1465G>A(p.Glu489Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000827 in 1,600,482 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00077 ( 6 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.467

Variant links:

Genes affected

FASN (HGNC:3594): (fatty acid synthase) The enzyme encoded by this gene is a multifunctional protein. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. In some cancer cell lines, this protein has been found to be fused with estrogen receptor-alpha (ER-alpha), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-alpha. [provided by RefSeq, Jul 2008]

FASN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055253804).

BP6

Variant 17-82091249-C-T is Benign according to our data. Variant chr17-82091249-C-T is described in ClinVar as [Benign]. Clinvar id is 462005.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 211 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.1465G>A	p.Glu489Lys	missense_variant	9/43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3 linkuse as main transcript	c.1465G>A	p.Glu489Lys	missense_variant	9/43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 linkuse as main transcript	c.1465G>A	p.Glu489Lys	missense_variant	9/43	1	NM_004104.5	ENSP00000304592	P1
FASN	ENST00000634990.1 linkuse as main transcript	c.1465G>A	p.Glu489Lys	missense_variant	9/43	5		ENSP00000488964

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00131

AC:

301

AN:

228944

Hom.:

AF XY:

0.00158

AC XY:

199

AN XY:

125674

show subpopulations

Gnomad AFR exome

AF:

0.00284

Gnomad AMR exome

AF:

0.000505

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000566

Gnomad SAS exome

AF:

0.00727

Gnomad FIN exome

AF:

0.000173

Gnomad NFE exome

AF:

0.000187

Gnomad OTH exome

AF:

0.00106

GnomAD4 exome

AF:

0.000769

AC:

1113

AN:

1448156

Hom.:

Cov.:

AF XY:

0.000979

AC XY:

704

AN XY:

719134

show subpopulations

Gnomad4 AFR exome

AF:

0.00363

Gnomad4 AMR exome

AF:

0.000566

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.00652

Gnomad4 FIN exome

AF:

0.0000824

Gnomad4 NFE exome

AF:

0.000331

Gnomad4 OTH exome

AF:

0.000568

GnomAD4 genome

AF:

0.00139

AC:

211

AN:

152326

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00358

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000495

Hom.:

Bravo

AF:

0.00126

ESP6500AA

AF:

0.00392

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00142

AC:

170

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FASN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 10, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.17

DANN

Benign

0.88

DEOGEN2

Benign

0.23

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.3

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.16

N;.

REVEL

Benign

0.077

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.21

MVP

0.36

ClinPred

0.0016

GERP RS

-5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.098

gMVP

0.37

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