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17-82091484-C-T

Variant summary

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

The NM_004104.5(FASN):c.1230G>A(p.Pro410=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,604,302 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P410P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

FASN
NM_004104.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.95
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 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=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-82091484-C-T is Benign according to our data. Variant chr17-82091484-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 462000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=-1.95 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 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FASNNM_004104.5 linkuse as main transcriptc.1230G>A p.Pro410= synonymous_variant 9/43 ENST00000306749.4
FASNXM_011523538.3 linkuse as main transcriptc.1230G>A p.Pro410= synonymous_variant 9/43

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FASNENST00000306749.4 linkuse as main transcriptc.1230G>A p.Pro410= synonymous_variant 9/431 NM_004104.5 P1
FASNENST00000634990.1 linkuse as main transcriptc.1230G>A p.Pro410= synonymous_variant 9/435

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000210
AC:
32
AN:
152066
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000386
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00251
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000295
AC:
66
AN:
223716
Hom.:
0
AF XY:
0.000262
AC XY:
32
AN XY:
122354
show subpopulations
Gnomad AFR exome
AF:
0.000362
Gnomad AMR exome
AF:
0.0000614
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00304
Gnomad SAS exome
AF:
0.000171
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000103
Gnomad OTH exome
AF:
0.000179
GnomAD4 exome
AF:
0.0000999
AC:
145
AN:
1452118
Hom.:
0
Cov.:
35
AF XY:
0.0000790
AC XY:
57
AN XY:
721804
show subpopulations
Gnomad4 AFR exome
AF:
0.000330
Gnomad4 AMR exome
AF:
0.000138
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00171
Gnomad4 SAS exome
AF:
0.000188
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000253
Gnomad4 OTH exome
AF:
0.000267
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000217
AC:
33
AN:
152184
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00251
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000212
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

FASN-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 09, 2019This 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 submitterclinical testingInvitaeDec 13, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
6.6
Dann
Benign
0.66
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6

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: rs376870564; hg19: chr17-80049360; API