rs150915750

Positions:

chr17-82085630-G-A

Variant summary

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

The NM_004104.5(FASN):c.3974C>T(p.Pro1325Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00174 in 1,596,154 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 9 hom. )

Consequence

FASN
NM_004104.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.50

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:

FASN (HGNC:):

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=0.010358661).

BP6

Variant 17-82085630-G-A is Benign according to our data. Variant chr17-82085630-G-A is described in ClinVar as [Benign]. Clinvar id is 462048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82085630-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 216 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.3974C>T	p.Pro1325Leu	missense_variant	23/43	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 linkuse as main transcript	c.3974C>T	p.Pro1325Leu	missense_variant	23/43		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FASN	ENST00000306749.4 linkuse as main transcript	c.3974C>T	p.Pro1325Leu	missense_variant	23/43	1	NM_004104.5	ENSP00000304592.2	P49327
FASN	ENST00000634990.1 linkuse as main transcript	c.3968C>T	p.Pro1323Leu	missense_variant	23/43	5		ENSP00000488964.1	A0A0U1RQF0
FASN	ENST00000579410.1 linkuse as main transcript	n.31C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

216

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00329

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00151

AC:

325

AN:

215482

Hom.:

AF XY:

0.00165

AC XY:

194

AN XY:

117496

show subpopulations

Gnomad AFR exome

AF:

0.000476

Gnomad AMR exome

AF:

0.000284

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.00350

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00178

AC:

2565

AN:

1443866

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1270

AN XY:

716920

show subpopulations

Gnomad4 AFR exome

AF:

0.000424

Gnomad4 AMR exome

AF:

0.000446

Gnomad4 ASJ exome

AF:

0.0000775

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.00178

Gnomad4 FIN exome

AF:

0.00281

Gnomad4 NFE exome

AF:

0.00193

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00142

AC:

216

AN:

152288

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00329

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00177

Hom.:

Bravo

AF:

0.00106

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000934

AC:

ExAC

AF:

0.00114

AC:

136

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

FASN-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2021

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.

Eigen

Benign

-0.066

Eigen_PC

Benign

-0.078

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.17

Sift

Benign

0.077

T;.

Sift4G

Benign

0.25

T;T

Polyphen

0.87

P;.

Vest4

0.58

MVP

0.35

ClinPred

0.036

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.21

gMVP

0.80

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