Variant rs2229425 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004104.5(FASN):c.5268C>T(p.Ser1756Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,612,004 control chromosomes in the GnomAD database, including 17,552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1085 hom., cov: 34)

Exomes 𝑓: 0.14 ( 16467 hom. )

Consequence

FASN
NM_004104.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0990

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 17-82083590-G-A is Benign according to our data. Variant chr17-82083590-G-A is described in ClinVar as [Benign]. Clinvar id is 1165094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.099 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.5268C>T	p.Ser1756Ser	synonymous_variant	31/43	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 linkuse as main transcript	c.5268C>T	p.Ser1756Ser	synonymous_variant	31/43		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 linkuse as main transcript	c.5268C>T	p.Ser1756Ser	synonymous_variant	31/43	1	NM_004104.5	ENSP00000304592.2		P49327
FASN	ENST00000634990.1 linkuse as main transcript	c.5262C>T	p.Ser1754Ser	synonymous_variant	31/43	5		ENSP00000488964.1		A0A0U1RQF0

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15491

AN:

152162

Hom.:

1087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0274

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0773

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0499

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.0989

GnomAD3 exomes

AF:

0.104

AC:

25716

AN:

246688

Hom.:

1842

AF XY:

0.106

AC XY:

14294

AN XY:

134216

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.0498

Gnomad ASJ exome

AF:

0.0492

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0496

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.141

AC:

206248

AN:

1459724

Hom.:

16467

Cov.:

AF XY:

0.139

AC XY:

100712

AN XY:

726070

show subpopulations

Gnomad4 AFR exome

AF:

0.0211

Gnomad4 AMR exome

AF:

0.0517

Gnomad4 ASJ exome

AF:

0.0511

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0503

Gnomad4 FIN exome

AF:

0.151

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.102

AC:

15486

AN:

152280

Hom.:

1085

Cov.:

AF XY:

0.0998

AC XY:

7432

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0273

Gnomad4 AMR

AF:

0.0772

Gnomad4 ASJ

AF:

0.0499

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0502

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.0974

Alfa

AF:

0.136

Hom.:

1857

Bravo

AF:

0.0925

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 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

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.6

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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