Variant rs2229426 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004104.5(FASN):c.5336C>T(p.Pro1779Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0103 in 1,612,814 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 9 hom., cov: 34)

Exomes 𝑓: 0.010 ( 79 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.31

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008900583).

BP6

Variant 17-82083522-G-A is Benign according to our data. Variant chr17-82083522-G-A is described in ClinVar as [Benign]. Clinvar id is 462068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82083522-G-A is described in Lovd as [Likely_benign]. Variant chr17-82083522-G-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 1314 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.5336C>T	p.Pro1779Leu	missense_variant	31/43	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 link	c.5336C>T	p.Pro1779Leu	missense_variant	31/43		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 link	c.5336C>T	p.Pro1779Leu	missense_variant	31/43	1	NM_004104.5	ENSP00000304592.2		P49327
FASN	ENST00000634990.1 link	c.5330C>T	p.Pro1777Leu	missense_variant	31/43	5		ENSP00000488964.1		A0A0U1RQF0

Frequencies

GnomAD3 genomes

AF:

0.00862

AC:

1313

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00856

AC:

2136

AN:

249424

Hom.:

AF XY:

0.00853

AC XY:

1155

AN XY:

135466

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00547

Gnomad ASJ exome

AF:

0.00652

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00140

Gnomad FIN exome

AF:

0.0196

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0100

GnomAD4 exome

AF:

0.0105

AC:

15309

AN:

1460434

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

7418

AN XY:

726514

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00586

Gnomad4 ASJ exome

AF:

0.00620

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00155

Gnomad4 FIN exome

AF:

0.0193

Gnomad4 NFE exome

AF:

0.0118

Gnomad4 OTH exome

AF:

0.00853

GnomAD4 genome

AF:

0.00862

AC:

1314

AN:

152380

Hom.:

Cov.:

AF XY:

0.00876

AC XY:

653

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00228

Gnomad4 AMR

AF:

0.00653

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00165

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00925

Hom.:

Bravo

AF:

0.00713

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0107

AC:

ExAC

AF:

0.00801

AC:

970

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0120

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	FASN: BP4, BS1, BS2 -

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 02, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Uncertain

0.45

T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.0089

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.8

D;.

REVEL

Benign

0.071

Sift

Benign

0.043

D;.

Sift4G

Uncertain

0.048

D;D

Polyphen

0.033

B;.

Vest4

0.15

MVP

0.30

ClinPred

0.036

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.090

gMVP

0.76

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