Variant rs45557233 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004104.5(FASN):c.4999C>T(p.Pro1667Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00375 in 1,553,648 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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. P1667P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0056 ( 59 hom., cov: 34)

Exomes 𝑓: 0.0035 ( 267 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.98

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039016604).

BP6

Variant 17-82084074-G-A is Benign according to our data. Variant chr17-82084074-G-A is described in ClinVar as [Benign]. Clinvar id is 462063.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82084074-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.4999C>T	p.Pro1667Ser	missense_variant	29/43	ENST00000306749.4
FASN	XM_011523538.3 linkuse as main transcript	c.4999C>T	p.Pro1667Ser	missense_variant	29/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASN	ENST00000306749.4 linkuse as main transcript	c.4999C>T	p.Pro1667Ser	missense_variant	29/43	1	NM_004104.5	P1
FASN	ENST00000634990.1 linkuse as main transcript	c.4993C>T	p.Pro1665Ser	missense_variant	29/43	5

Frequencies

GnomAD3 genomes

AF:

0.00558

AC:

850

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.0124

AC:

1881

AN:

151084

Hom.:

125

AF XY:

0.0120

AC XY:

977

AN XY:

81610

show subpopulations

Gnomad AFR exome

AF:

0.00152

Gnomad AMR exome

AF:

0.000558

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.00505

Gnomad FIN exome

AF:

0.0000735

Gnomad NFE exome

AF:

0.0000694

Gnomad OTH exome

AF:

0.00691

GnomAD4 exome

AF:

0.00355

AC:

4970

AN:

1401316

Hom.:

267

Cov.:

AF XY:

0.00366

AC XY:

2536

AN XY:

691978

show subpopulations

Gnomad4 AFR exome

AF:

0.000849

Gnomad4 AMR exome

AF:

0.000414

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.00656

Gnomad4 FIN exome

AF:

0.000218

Gnomad4 NFE exome

AF:

0.0000517

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00559

AC:

851

AN:

152332

Hom.:

Cov.:

AF XY:

0.00626

AC XY:

466

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.135

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.000825

Hom.:

Bravo

AF:

0.00671

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00191

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00570

AC:

635

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Benign

0.75

DEOGEN2

Benign

0.34

T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.69

N;.

REVEL

Benign

0.064

Sift

Benign

0.46

T;.

Sift4G

Benign

0.50

T;T

Polyphen

0.081

B;.

Vest4

0.28

ClinPred

0.0043

GERP RS

2.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.11

gMVP

0.56

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