chr17-82083019-T-C

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.5662A>G(p.Ile1888Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,612,872 control chromosomes in the GnomAD database, including 319 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 (★★).

Frequency

Genomes: 𝑓 0.026 ( 150 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 169 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0370

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032187104).

BP6

Variant 17-82083019-T-C is Benign according to our data. Variant chr17-82083019-T-C is described in CliVar as Benign. Clinvar id is 462079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82083019-T-C is described in CliVar as Benign. Clinvar id is 462079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82083019-T-C is described in CliVar as Benign. Clinvar id is 462079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82083019-T-C is described in CliVar as Benign. Clinvar id is 462079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82083019-T-C is described in CliVar as Benign. Clinvar id is 462079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82083019-T-C is described in CliVar as Benign. Clinvar id is 462079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82083019-T-C is described in CliVar as Benign. Clinvar id is 462079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82083019-T-C is described in CliVar as Benign. Clinvar id is 462079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82083019-T-C is described in CliVar as Benign. Clinvar id is 462079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.5662A>G	p.Ile1888Val	missense_variant	Exon 33 of 43	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 link	c.5662A>G	p.Ile1888Val	missense_variant	Exon 33 of 43		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 link	c.5662A>G	p.Ile1888Val	missense_variant	Exon 33 of 43	1	NM_004104.5	ENSP00000304592.2		P49327
FASN	ENST00000634990.1 link	c.5656A>G	p.Ile1886Val	missense_variant	Exon 33 of 43	5		ENSP00000488964.1		A0A0U1RQF0

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3987

AN:

152096

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.00715

AC:

1789

AN:

250062

AF XY:

0.00516

show subpopulations

Gnomad AFR exome

AF:

0.0962

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000284

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00276

AC:

4030

AN:

1460658

Hom.:

169

Cov.:

AF XY:

0.00249

AC XY:

1810

AN XY:

726626

show subpopulations

African (AFR)

AF:

0.0963

AC:

3225

AN:

33478

American (AMR)

AF:

0.00572

AC:

256

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000185

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52250

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000112

AC:

125

AN:

1111980

Other (OTH)

AF:

0.00641

AC:

387

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

279

557

836

1114

1393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.0264

AC:

4017

AN:

152214

Hom.:

150

Cov.:

AF XY:

0.0254

AC XY:

1891

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0917

AC:

3807

AN:

41514

American (AMR)

AF:

0.0107

AC:

163

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68000

Other (OTH)

AF:

0.0137

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

188

376

564

752

940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0121

Hom.:

127

Bravo

AF:

0.0302

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0873

AC:

384

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00871

AC:

1056

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Feb 03, 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

0.084

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.021

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.21

N;.

PhyloP100

0.037

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.49

N;.

REVEL

Benign

0.044

Sift

Benign

0.53

T;.

Sift4G

Benign

0.52

T;T

Polyphen

0.0050

B;.

Vest4

0.099

MVP

0.23

ClinPred

0.0025

GERP RS

-8.2

Varity_R

0.048

gMVP

0.39

Mutation Taster

=69/31

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