rs200366210
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_004104.5(FASN):c.966C>T(p.Ile322=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,604,152 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 1 hom. )
Consequence
FASN
NM_004104.5 synonymous
NM_004104.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0620
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
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 17-82092518-G-A is Benign according to our data. Variant chr17-82092518-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 531084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.062 with no splicing effect.
BS2
?
High AC in GnomAd4 at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.966C>T | p.Ile322= | synonymous_variant | 8/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.966C>T | p.Ile322= | synonymous_variant | 8/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.966C>T | p.Ile322= | synonymous_variant | 8/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.966C>T | p.Ile322= | synonymous_variant | 8/43 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000530 AC: 121AN: 228090Hom.: 1 AF XY: 0.000526 AC XY: 66AN XY: 125388
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GnomAD4 exome AF: 0.000178 AC: 258AN: 1451864Hom.: 1 Cov.: 37 AF XY: 0.000188 AC XY: 136AN XY: 721952
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
FASN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 04, 2019 | This 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 submitter | clinical testing | Invitae | Dec 14, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | FASN: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at