Variant rs143618212 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000306749.4(FASN):c.694C>T(p.Leu232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000471 in 1,612,220 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 1 hom. )

Consequence

FASN
ENST00000306749.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.953

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 made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 17-82092981-G-A is Benign according to our data. Variant chr17-82092981-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 462105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82092981-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.953 with no splicing effect.

BS2

High AC in GnomAd4 at 61 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.694C>T	p.Leu232=	synonymous_variant	6/43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3 linkuse as main transcript	c.694C>T	p.Leu232=	synonymous_variant	6/43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 linkuse as main transcript	c.694C>T	p.Leu232=	synonymous_variant	6/43	1	NM_004104.5	ENSP00000304592	P1
FASN	ENST00000634990.1 linkuse as main transcript	c.694C>T	p.Leu232=	synonymous_variant	6/43	5		ENSP00000488964

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000612

AC:

151

AN:

246890

Hom.:

AF XY:

0.000729

AC XY:

AN XY:

134408

show subpopulations

Gnomad AFR exome

AF:

0.000191

Gnomad AMR exome

AF:

0.000378

Gnomad ASJ exome

AF:

0.000302

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000711

Gnomad OTH exome

AF:

0.000999

GnomAD4 exome

AF:

0.000479

AC:

699

AN:

1459884

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

371

AN XY:

726178

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.000456

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.000400

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000610

Hom.:

Bravo

AF:

0.000363

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000949

ClinVar

Significance: Benign/Likely 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

Mar 11, 2019

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

FASN: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.0

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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