17-82084703-C-T

Variant names:

• chr17-82084703-C-T
• rs45483502
• NM_004104.5:c.4578G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004104.5(FASN):​c.4578G>A​(p.Glu1526Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,564,892 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (69 hom., cov: 34)
  • Exomes 𝑓: 0.0016 (65 hom.)
• Consequence: FASN NM_004104.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-82084703-C-T is Benign according to our data. Variant chr17-82084703-C-T is described in ClinVar as Benign. ClinVar VariationId is 462058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004104.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASN	NM_004104.5	MANE Select	c.4578G>A	p.Glu1526Glu	synonymous	Exon 27 of 43	NP_004095.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASN	ENST00000306749.4	TSL:1 MANE Select	c.4578G>A	p.Glu1526Glu	synonymous	Exon 27 of 43	ENSP00000304592.2
	FASN	ENST00000634990.1	TSL:5	c.4572G>A	p.Glu1524Glu	synonymous	Exon 27 of 43	ENSP00000488964.1

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2481 AN: 152248 Hom.: 69 Cov.: 34

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00376 AC: 651 AN: 173008 AF XY: 0.00272

Gnomad AFR exome AF: 0.0574

Gnomad AMR exome AF: 0.00298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000423

Gnomad OTH exome AF: 0.00106

GnomAD4 exome AF: 0.00156 AC: 2208 AN: 1412526 Hom.: 65 Cov.: 42 AF XY: 0.00134 AC XY: 935 AN XY: 698064

African (AFR) AF: 0.0572 AC: 1850 AN: 32318

American (AMR) AF: 0.00340 AC: 127 AN: 37336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25318

East Asian (EAS) AF: 0.00 AC: 0 AN: 36832

South Asian (SAS) AF: 0.0000743 AC: 6 AN: 80776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48716

Middle Eastern (MID) AF: 0.000875 AC: 5 AN: 5714

European-Non Finnish (NFE) AF: 0.0000193 AC: 21 AN: 1086984

Other (OTH) AF: 0.00340 AC: 199 AN: 58532

GnomAD4 genome AF: 0.0163 AC: 2486 AN: 152366 Hom.: 69 Cov.: 34 AF XY: 0.0157 AC XY: 1169 AN XY: 74516

African (AFR) AF: 0.0564 AC: 2344 AN: 41584

American (AMR) AF: 0.00745 AC: 114 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68032

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00920 Hom.: 18

Bravo AF: 0.0183

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

FASN-related disorder Benign:1

Apr 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Epileptic encephalopathy Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.9
DANN	Benign	0.79
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs45483502; hg19: chr17-80042579;