rs2229426

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.5336C>T(p.Pro1779Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0103 in 1,612,814 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1779A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0086 ( 9 hom., cov: 34)

Exomes 𝑓: 0.010 ( 79 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.31

Publications

7 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=0.008900583).

BP6

Variant 17-82083522-G-A is Benign according to our data. Variant chr17-82083522-G-A is described in ClinVar as [Benign]. Clinvar id is 462068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.5336C>T	p.Pro1779Leu	missense_variant	Exon 31 of 43	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 link	c.5336C>T	p.Pro1779Leu	missense_variant	Exon 31 of 43		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 link	c.5336C>T	p.Pro1779Leu	missense_variant	Exon 31 of 43	1	NM_004104.5	ENSP00000304592.2		P49327
FASN	ENST00000634990.1 link	c.5330C>T	p.Pro1777Leu	missense_variant	Exon 31 of 43	5		ENSP00000488964.1		A0A0U1RQF0

Frequencies

GnomAD3 genomes

AF:

0.00862

AC:

1313

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00856

AC:

2136

AN:

249424

AF XY:

0.00853

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00547

Gnomad ASJ exome

AF:

0.00652

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0196

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0100

GnomAD4 exome

AF:

0.0105

AC:

15309

AN:

1460434

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

7418

AN XY:

726514

show subpopulations

African (AFR)

AF:

0.00131

AC:

AN:

33480

American (AMR)

AF:

0.00586

AC:

262

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00620

AC:

162

AN:

26132

East Asian (EAS)

AF:

0.000151

AC:

AN:

39698

South Asian (SAS)

AF:

0.00155

AC:

134

AN:

86238

European-Finnish (FIN)

AF:

0.0193

AC:

1006

AN:

52066

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0118

AC:

13143

AN:

1111956

Other (OTH)

AF:

0.00853

AC:

515

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1133

2266

3400

4533

5666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.00862

AC:

1314

AN:

152380

Hom.:

Cov.:

AF XY:

0.00876

AC XY:

653

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.00228

AC:

AN:

41602

American (AMR)

AF:

0.00653

AC:

100

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00165

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0228

AC:

242

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

824

AN:

68026

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

140

211

281

351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0100

Hom.:

Bravo

AF:

0.00713

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0107

AC:

ExAC

AF:

0.00801

AC:

970

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0120

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FASN: BP4, BS1, BS2 -

Epileptic encephalopathy

Benign:1

Feb 02, 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

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Uncertain

0.45

T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.0089

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.

PhyloP100

4.3

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.8

D;.

REVEL

Benign

0.071

Sift

Benign

0.043

D;.

Sift4G

Uncertain

0.048

D;D

Polyphen

0.033

B;.

Vest4

0.15

MVP

0.30

ClinPred

0.036

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.090

gMVP

0.76

Mutation Taster

=94/6

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