17-82082574-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004104.5(FASN):c.5872G>A(p.Glu1958Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00594 in 1,609,570 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 32 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.84

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

FASN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01355502).

BP6

Variant 17-82082574-C-T is Benign according to our data. Variant chr17-82082574-C-T is described in ClinVar as Benign. ClinVar VariationId is 462083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.5872G>A	p.Glu1958Lys	missense_variant	Exon 34 of 43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3 link	c.5872G>A	p.Glu1958Lys	missense_variant	Exon 34 of 43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 link	c.5872G>A	p.Glu1958Lys	missense_variant	Exon 34 of 43	1	NM_004104.5	ENSP00000304592.2
FASN	ENST00000634990.1 link	c.5866G>A	p.Glu1956Lys	missense_variant	Exon 34 of 43	5		ENSP00000488964.1

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

675

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00695

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00376

AC:

917

AN:

243830

AF XY:

0.00372

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00954

Gnomad NFE exome

AF:

0.00566

Gnomad OTH exome

AF:

0.00234

GnomAD4 exome

AF:

0.00610

AC:

8882

AN:

1457210

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

4209

AN XY:

725184

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

33472

American (AMR)

AF:

0.00163

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00157

AC:

AN:

26104

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.000638

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00815

AC:

400

AN:

49070

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00713

AC:

7929

AN:

1111828

Other (OTH)

AF:

0.00550

AC:

332

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

560

1120

1681

2241

2801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

318

636

954

1272

1590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00442

AC:

674

AN:

152360

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

327

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00151

AC:

AN:

41586

American (AMR)

AF:

0.000980

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000866

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0107

AC:

114

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00695

AC:

473

AN:

68024

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

104

138

173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00426

Hom.:

Bravo

AF:

0.00370

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00583

AC:

ExAC

AF:

0.00346

AC:

417

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00583

EpiControl

AF:

0.00575

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

FASN-related disorder

Benign:1

Feb 21, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.4

L;.

PhyloP100

5.8

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.4

N;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.015

D;.

Sift4G

Benign

0.15

T;T

Polyphen

1.0

D;.

Vest4

0.72

MVP

0.47

ClinPred

0.016

GERP RS

4.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.2

Varity_R

0.67

gMVP

0.79

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over