rs115708196
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004104.5(FASN):c.5337G>A(p.Pro1779=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,612,620 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0061 ( 7 hom., cov: 34)
Exomes 𝑓: 0.00098 ( 16 hom. )
Consequence
FASN
NM_004104.5 synonymous
NM_004104.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -7.92
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 17-82083521-C-T is Benign according to our data. Variant chr17-82083521-C-T is described in ClinVar as [Benign]. Clinvar id is 462069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-7.92 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00613 (934/152340) while in subpopulation AFR AF= 0.0194 (808/41578). AF 95% confidence interval is 0.0183. There are 7 homozygotes in gnomad4. There are 443 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 934 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.5337G>A | p.Pro1779= | synonymous_variant | 31/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.5337G>A | p.Pro1779= | synonymous_variant | 31/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.5337G>A | p.Pro1779= | synonymous_variant | 31/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.5331G>A | p.Pro1777= | synonymous_variant | 31/43 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00613 AC: 933AN: 152220Hom.: 7 Cov.: 34
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GnomAD3 exomes AF: 0.00210 AC: 523AN: 249442Hom.: 3 AF XY: 0.00168 AC XY: 227AN XY: 135472
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GnomAD4 exome AF: 0.000984 AC: 1437AN: 1460280Hom.: 16 Cov.: 36 AF XY: 0.000889 AC XY: 646AN XY: 726446
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GnomAD4 genome ? AF: 0.00613 AC: 934AN: 152340Hom.: 7 Cov.: 34 AF XY: 0.00595 AC XY: 443AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
FASN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 09, 2019 | 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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