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GeneBe

rs147764458

chr17-82095351-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004104.5(FASN):c.249G>A(p.Leu83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000486 in 1,612,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

FASN
NM_004104.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.557
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-82095351-C-T is Benign according to our data. Variant chr17-82095351-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 462024.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.557 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 43 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FASNNM_004104.5 linkuse as main transcriptc.249G>A p.Leu83= synonymous_variant 3/43 ENST00000306749.4
FASNXM_011523538.3 linkuse as main transcriptc.249G>A p.Leu83= synonymous_variant 3/43

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FASNENST00000306749.4 linkuse as main transcriptc.249G>A p.Leu83= synonymous_variant 3/431 NM_004104.5 P1
FASNENST00000634990.1 linkuse as main transcriptc.249G>A p.Leu83= synonymous_variant 3/435
FASNENST00000635197.1 linkuse as main transcriptc.249G>A p.Leu83= synonymous_variant 3/43
FASNENST00000637525.1 linkuse as main transcriptn.26G>A non_coding_transcript_exon_variant 1/25

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000282
AC:
43
AN:
152244
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000723
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.000573
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000240
AC:
60
AN:
249658
Hom.:
0
AF XY:
0.000258
AC XY:
35
AN XY:
135598
show subpopulations
Gnomad AFR exome
AF:
0.0000624
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000480
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000507
AC:
741
AN:
1460540
Hom.:
0
Cov.:
34
AF XY:
0.000464
AC XY:
337
AN XY:
726570
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000384
Gnomad4 NFE exome
AF:
0.000631
Gnomad4 OTH exome
AF:
0.000414
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000282
AC:
43
AN:
152244
Hom.:
0
Cov.:
34
AF XY:
0.000242
AC XY:
18
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000723
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000573
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000488
Hom.:
0
Bravo
AF:
0.000295
EpiCase
AF:
0.000491
EpiControl
AF:
0.000889

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 12, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
9.6
Dann
Benign
0.96

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.

Other links and lift over

dbSNP: rs147764458; hg19: chr17-80053227; API