NM_004104.5:c.2155G>A

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.2155G>A(p.Glu719Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00625 in 1,567,442 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 43 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.54

Publications

9 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=0.007240474).

BP6

Variant 17-82089118-C-T is Benign according to our data. Variant chr17-82089118-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.2155G>A	p.Glu719Lys	missense_variant	Exon 14 of 43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3 link	c.2155G>A	p.Glu719Lys	missense_variant	Exon 14 of 43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 link	c.2155G>A	p.Glu719Lys	missense_variant	Exon 14 of 43	1	NM_004104.5	ENSP00000304592.2
FASN	ENST00000634990.1 link	c.2155G>A	p.Glu719Lys	missense_variant	Exon 14 of 43	5		ENSP00000488964.1

Frequencies

GnomAD3 genomes

AF:

0.00540

AC:

822

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00684

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00579

AC:

1021

AN:

176270

AF XY:

0.00573

show subpopulations

Gnomad AFR exome

AF:

0.00492

Gnomad AMR exome

AF:

0.00433

Gnomad ASJ exome

AF:

0.0276

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00669

Gnomad OTH exome

AF:

0.00545

GnomAD4 exome

AF:

0.00635

AC:

8980

AN:

1415158

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

4434

AN XY:

700194

show subpopulations

African (AFR)

AF:

0.00434

AC:

139

AN:

32016

American (AMR)

AF:

0.00414

AC:

157

AN:

37904

Ashkenazi Jewish (ASJ)

AF:

0.0277

AC:

703

AN:

25374

East Asian (EAS)

AF:

0.0000548

AC:

AN:

36484

South Asian (SAS)

AF:

0.00313

AC:

255

AN:

81368

European-Finnish (FIN)

AF:

0.00159

AC:

AN:

49056

Middle Eastern (MID)

AF:

0.00297

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00667

AC:

7261

AN:

1088612

Other (OTH)

AF:

0.00628

AC:

368

AN:

58622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

626

1252

1877

2503

3129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.00540

AC:

822

AN:

152284

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

390

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00419

AC:

174

AN:

41558

American (AMR)

AF:

0.00359

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00228

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00684

AC:

465

AN:

68006

Other (OTH)

AF:

0.00427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

131

175

219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00638

Hom.:

Bravo

AF:

0.00559

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00209

AC:

ESP6500EA

AF:

0.00786

AC:

ExAC

AF:

0.00417

AC:

494

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 02, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FASN: BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Epileptic encephalopathy

Benign:1

Jan 23, 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

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.48

T;.

Eigen

Benign

0.099

Eigen_PC

Benign

0.059

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0072

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

L;.

PhyloP100

4.5

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.3

N;.

REVEL

Benign

0.17

Sift

Benign

0.067

T;.

Sift4G

Uncertain

0.060

T;T

Polyphen

1.0

D;.

Vest4

0.46

MVP

0.49

ClinPred

0.026

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.42

gMVP

0.69

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: -3

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