Variant 17-82082544-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.5902G>A(p.Val1968Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,608,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.175

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=0.011793315).

BP6

Variant 17-82082544-C-T is Benign according to our data. Variant chr17-82082544-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 531135.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.5902G>A	p.Val1968Ile	missense_variant	34/43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3 linkuse as main transcript	c.5902G>A	p.Val1968Ile	missense_variant	34/43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 linkuse as main transcript	c.5902G>A	p.Val1968Ile	missense_variant	34/43	1	NM_004104.5	ENSP00000304592	P1
FASN	ENST00000634990.1 linkuse as main transcript	c.5896G>A	p.Val1966Ile	missense_variant	34/43	5		ENSP00000488964

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000144

AC:

AN:

242614

Hom.:

AF XY:

0.000113

AC XY:

AN XY:

132984

show subpopulations

Gnomad AFR exome

AF:

0.00140

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000547

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000996

AC:

145

AN:

1456196

Hom.:

Cov.:

AF XY:

0.0000980

AC XY:

AN XY:

724736

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000208

Gnomad4 NFE exome

AF:

0.0000774

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000440

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000107

Hom.:

Bravo

AF:

0.000548

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000158

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.28

DANN

Benign

0.34

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.0045

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.22

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

0.28

N;.

REVEL

Benign

0.072

Sift

Benign

0.88

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0030

B;.

Vest4

0.15

MVP

0.21

ClinPred

0.00099

GERP RS

-4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Varity_R

0.045

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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