chr17-82090395-G-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.1850C>T(p.Pro617Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00139 in 1,593,704 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P617R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 6 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 3.89

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026117533).

BP6

Variant 17-82090395-G-A is Benign according to our data. Variant chr17-82090395-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 462012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 127 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.1850C>T	p.Pro617Leu	missense_variant	Exon 11 of 43	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 link	c.1850C>T	p.Pro617Leu	missense_variant	Exon 11 of 43		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 link	c.1850C>T	p.Pro617Leu	missense_variant	Exon 11 of 43	1	NM_004104.5	ENSP00000304592.2		P49327
FASN	ENST00000634990.1 link	c.1850C>T	p.Pro617Leu	missense_variant	Exon 11 of 43	5		ENSP00000488964.1		A0A0U1RQF0

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000925

AC:

198

AN:

213948

AF XY:

0.000957

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.000914

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.00128

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00144

AC:

2081

AN:

1441412

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1011

AN XY:

715100

show subpopulations

African (AFR)

AF:

0.000271

AC:

AN:

33254

American (AMR)

AF:

0.00106

AC:

AN:

41364

Ashkenazi Jewish (ASJ)

AF:

0.0000391

AC:

AN:

25584

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38910

South Asian (SAS)

AF:

0.0000360

AC:

AN:

83352

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

50392

Middle Eastern (MID)

AF:

0.000183

AC:

AN:

5454

European-Non Finnish (NFE)

AF:

0.00170

AC:

1874

AN:

1103582

Other (OTH)

AF:

0.00121

AC:

AN:

59520

Heterozygous variant carriers

118

236

353

471

589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152292

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41558

American (AMR)

AF:

0.000784

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00138

AC:

AN:

67990

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.00118

Hom.:

Bravo

AF:

0.000918

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000462

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000701

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpretted as Uncertain significance and reported on 06/15/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

FASN-related disorder

Benign:1

Mar 28, 2022

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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Uncertain

0.48

T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.026

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.093

Sift

Benign

0.18

T;.

Sift4G

Benign

0.37

T;T

Polyphen

0.0020

B;.

Vest4

0.23

MVP

0.24

ClinPred

0.018

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.15

gMVP

0.71

Mutation Taster

=97/3

polymorphism

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over