rs150915750

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.3974C>T(p.Pro1325Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00174 in 1,596,154 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1325P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 9 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.50

Publications

3 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=0.010358661).

BP6

Variant 17-82085630-G-A is Benign according to our data. Variant chr17-82085630-G-A is described in ClinVar as Benign. ClinVar VariationId is 462048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.3974C>T	p.Pro1325Leu	missense_variant	Exon 23 of 43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3 link	c.3974C>T	p.Pro1325Leu	missense_variant	Exon 23 of 43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
FASN	ENST00000306749.4 link	c.3974C>T	p.Pro1325Leu	missense_variant	Exon 23 of 43	1	NM_004104.5	ENSP00000304592.2
FASN	ENST00000634990.1 link	c.3968C>T	p.Pro1323Leu	missense_variant	Exon 23 of 43	5		ENSP00000488964.1
FASN	ENST00000579410.1 link	n.31C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

216

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00329

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00151

AC:

325

AN:

215482

AF XY:

0.00165

show subpopulations

Gnomad AFR exome

AF:

0.000476

Gnomad AMR exome

AF:

0.000284

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00350

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00178

AC:

2565

AN:

1443866

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1270

AN XY:

716920

show subpopulations

African (AFR)

AF:

0.000424

AC:

AN:

33044

American (AMR)

AF:

0.000446

AC:

AN:

42572

Ashkenazi Jewish (ASJ)

AF:

0.0000775

AC:

AN:

25800

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38652

South Asian (SAS)

AF:

0.00178

AC:

149

AN:

83582

European-Finnish (FIN)

AF:

0.00281

AC:

142

AN:

50590

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00193

AC:

2135

AN:

1104236

Other (OTH)

AF:

0.00161

AC:

AN:

59638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

190

380

569

759

949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.00142

AC:

216

AN:

152288

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41558

American (AMR)

AF:

0.00131

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00187

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00329

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00193

AC:

131

AN:

68010

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

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:

0.00170

Hom.:

Bravo

AF:

0.00106

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000934

AC:

ExAC

AF:

0.00114

AC:

136

Asia WGS

AF:

0.000577

AC:

AN:

3478

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 22, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely 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 08, 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

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.

Eigen

Benign

-0.066

Eigen_PC

Benign

-0.078

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

PhyloP100

6.5

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.17

Sift

Benign

0.077

T;.

Sift4G

Benign

0.25

T;T

Vest4

0.58

ClinPred

0.036

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.21

gMVP

0.80

Mutation Taster

=87/13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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