17-82084916-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004104.5(FASN):c.4447G>A(p.Val1483Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 1,551,942 control chromosomes in the GnomAD database, including 1,238 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. V1483L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.045 ( 191 hom., cov: 34)

Exomes 𝑓: 0.034 ( 1047 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.01

Publications

28 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00211218).

BP6

Variant 17-82084916-C-T is Benign according to our data. Variant chr17-82084916-C-T is described in CliVar as Benign. Clinvar id is 1167210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82084916-C-T is described in CliVar as Benign. Clinvar id is 1167210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82084916-C-T is described in CliVar as Benign. Clinvar id is 1167210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82084916-C-T is described in CliVar as Benign. Clinvar id is 1167210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82084916-C-T is described in CliVar as Benign. Clinvar id is 1167210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82084916-C-T is described in CliVar as Benign. Clinvar id is 1167210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82084916-C-T is described in CliVar as Benign. Clinvar id is 1167210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82084916-C-T is described in CliVar as Benign. Clinvar id is 1167210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82084916-C-T is described in CliVar as Benign. Clinvar id is 1167210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.4447G>A	p.Val1483Ile	missense_variant	Exon 26 of 43	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 link	c.4447G>A	p.Val1483Ile	missense_variant	Exon 26 of 43		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FASN	ENST00000306749.4 link	c.4447G>A	p.Val1483Ile	missense_variant	Exon 26 of 43	1	NM_004104.5	ENSP00000304592.2	P49327
FASN	ENST00000634990.1 link	c.4441G>A	p.Val1481Ile	missense_variant	Exon 26 of 43	5		ENSP00000488964.1	A0A0U1RQF0
FASN	ENST00000579410.1 link	n.*242G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6835

AN:

151772

Hom.:

190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0755

Gnomad AMI

AF:

0.0848

Gnomad AMR

AF:

0.0433

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00272

Gnomad SAS

AF:

0.0865

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0307

Gnomad OTH

AF:

0.0403

GnomAD2 exomes

AF:

0.0415

AC:

6577

AN:

158660

AF XY:

0.0429

show subpopulations

Gnomad AFR exome

AF:

0.0772

Gnomad AMR exome

AF:

0.0514

Gnomad ASJ exome

AF:

0.0382

Gnomad EAS exome

AF:

0.00327

Gnomad FIN exome

AF:

0.0239

Gnomad NFE exome

AF:

0.0301

Gnomad OTH exome

AF:

0.0384

GnomAD4 exome

AF:

0.0339

AC:

47524

AN:

1400048

Hom.:

1047

Cov.:

AF XY:

0.0349

AC XY:

24092

AN XY:

690816

show subpopulations

African (AFR)

AF:

0.0746

AC:

2369

AN:

31770

American (AMR)

AF:

0.0520

AC:

1865

AN:

35868

Ashkenazi Jewish (ASJ)

AF:

0.0370

AC:

931

AN:

25174

East Asian (EAS)

AF:

0.00159

AC:

AN:

35936

South Asian (SAS)

AF:

0.0802

AC:

6380

AN:

79544

European-Finnish (FIN)

AF:

0.0247

AC:

1184

AN:

48024

Middle Eastern (MID)

AF:

0.0264

AC:

150

AN:

5690

European-Non Finnish (NFE)

AF:

0.0299

AC:

32301

AN:

1079988

Other (OTH)

AF:

0.0394

AC:

2287

AN:

58054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

3067

6133

9200

12266

15333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1302

2604

3906

5208

6510

<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:

0.0450

AC:

6841

AN:

151894

Hom.:

191

Cov.:

AF XY:

0.0439

AC XY:

3263

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.0754

AC:

3121

AN:

41410

American (AMR)

AF:

0.0434

AC:

663

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3470

East Asian (EAS)

AF:

0.00272

AC:

AN:

5140

South Asian (SAS)

AF:

0.0870

AC:

417

AN:

4794

European-Finnish (FIN)

AF:

0.0216

AC:

228

AN:

10550

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0307

AC:

2083

AN:

67944

Other (OTH)

AF:

0.0404

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

327

654

982

1309

1636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0330

Hom.:

263

Bravo

AF:

0.0470

TwinsUK

AF:

0.0310

AC:

115

ALSPAC

AF:

0.0304

AC:

117

ESP6500AA

AF:

0.0661

AC:

271

ESP6500EA

AF:

0.0250

AC:

203

ExAC

AF:

0.0251

AC:

2727

Asia WGS

AF:

0.0530

AC:

187

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Feb 04, 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

0.072

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.015

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

N;.

PhyloP100

-1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.040

N;.

REVEL

Benign

0.021

Sift

Benign

0.51

T;.

Sift4G

Benign

0.51

T;T

Polyphen

0.012

B;.

Vest4

0.071

ClinPred

0.00043

GERP RS

-1.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.065

gMVP

0.15

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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