chr17-82082544-C-T

Variant names:

• chr17-82082544-C-T
• rs148731010
• NM_004104.5:c.5902G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004104.5(FASN):​c.5902G>A​(p.Val1968Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,608,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. V1968V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: FASN NM_004104.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.175
• Publications: 4 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011793315).
• BP6: Variant 17-82082544-C-T is Benign according to our data. Variant chr17-82082544-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 531135.Status of the report is criteria_provided_single_submitter, 1 stars.

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.5902G>A	p.Val1968Ile	missense	Exon 34 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.5902G>A	p.Val1968Ile	missense	Exon 34 of 43	ENSP00000304592.2
	FASN	ENST00000634990.1	TSL:5	c.5896G>A	p.Val1966Ile	missense	Exon 34 of 43	ENSP00000488964.1

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 65 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000144 AC: 35 AN: 242614 AF XY: 0.000113

Gnomad AFR exome AF: 0.00140

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000166

Gnomad FIN exome AF: 0.0000547

Gnomad NFE exome AF: 0.0000272

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000996 AC: 145 AN: 1456196 Hom.: 0 Cov.: 38 AF XY: 0.0000980 AC XY: 71 AN XY: 724736

African (AFR) AF: 0.00117 AC: 39 AN: 33474

American (AMR) AF: 0.000157 AC: 7 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.0000208 AC: 1 AN: 48110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000774 AC: 86 AN: 1111782

Other (OTH) AF: 0.000149 AC: 9 AN: 60334

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152336 Hom.: 0 Cov.: 33 AF XY: 0.000416 AC XY: 31 AN XY: 74486

African (AFR) AF: 0.00123 AC: 51 AN: 41572

American (AMR) AF: 0.000784 AC: 12 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000319 Hom.: 0

Bravo AF: 0.000548

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000158 AC: 19

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epileptic encephalopathy Benign:1

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.28
DANN	Benign	0.34
DEOGEN2	Benign	0.25	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.22	N
PhyloP100		0.17
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.072
Sift	Benign	0.88	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.15
MVP		0.21
ClinPred		0.00099	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Varity_R		0.045
gMVP		0.22
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148731010; hg19: chr17-80040420;