rs17848945

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004104.5(FASN):c.5809G>A(p.Val1937Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,610,686 control chromosomes in the GnomAD database, including 37 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 0.00070 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 35 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.195

Publications

12 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044974387).

BP6

Variant 17-82082637-C-T is Benign according to our data. Variant chr17-82082637-C-T is described in ClinVar as Benign. ClinVar VariationId is 531128.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00106 (1543/1458374) while in subpopulation EAS AF = 0.0312 (1237/39694). AF 95% confidence interval is 0.0297. There are 35 homozygotes in GnomAdExome4. There are 779 alleles in the male GnomAdExome4 subpopulation. Median coverage is 38. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004104.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASN	NM_004104.5	MANE Select	c.5809G>A	p.Val1937Ile	missense	Exon 34 of 43	NP_004095.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FASN	ENST00000306749.4	TSL:1 MANE Select	c.5809G>A	p.Val1937Ile	missense	Exon 34 of 43	ENSP00000304592.2	P49327
FASN	ENST00000940344.1		c.5836G>A	p.Val1946Ile	missense	Exon 34 of 43	ENSP00000610403.1
FASN	ENST00000940346.1		c.5833G>A	p.Val1945Ile	missense	Exon 34 of 43	ENSP00000610405.1

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0150

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00125

AC:

306

AN:

245486

AF XY:

0.00122

show subpopulations

Gnomad AFR exome

AF:

0.0000638

Gnomad AMR exome

AF:

0.000580

Gnomad ASJ exome

AF:

0.00141

Gnomad EAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.000828

GnomAD4 exome

AF:

0.00106

AC:

1543

AN:

1458374

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

779

AN XY:

725692

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33474

American (AMR)

AF:

0.000514

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

26118

East Asian (EAS)

AF:

0.0312

AC:

1237

AN:

39694

South Asian (SAS)

AF:

0.00115

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50158

Middle Eastern (MID)

AF:

0.000695

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000854

AC:

AN:

1111858

Other (OTH)

AF:

0.000862

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

110

219

329

438

548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000696

AC:

106

AN:

152312

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41576

American (AMR)

AF:

0.000457

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0149

AC:

AN:

5178

South Asian (SAS)

AF:

0.00228

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68014

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.000888

Hom.:

Bravo

AF:

0.000774

ExAC

AF:

0.00128

AC:

154

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.6

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.27

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.20

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.24

REVEL

Benign

0.055

Sift

Benign

0.92

Sift4G

Benign

0.47

Polyphen

0.051

Vest4

0.16

MVP

0.24

ClinPred

0.0049

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.37

Mutation Taster

=97/3

polymorphism

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over