chr17-82086304-G-A
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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.3682C>T(p.Leu1228=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,598,490 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0092 ( 21 hom., cov: 33)
Exomes 𝑓: 0.00098 ( 31 hom. )
Consequence
FASN
NM_004104.5 synonymous
NM_004104.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.11
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=-0.56).
BP6
Variant 17-82086304-G-A is Benign according to our data. Variant chr17-82086304-G-A is described in ClinVar as [Benign]. Clinvar id is 462042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.11 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00918 (1398/152358) while in subpopulation AFR AF= 0.0318 (1323/41590). AF 95% confidence interval is 0.0304. There are 21 homozygotes in gnomad4. There are 644 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1398 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.3682C>T | p.Leu1228= | synonymous_variant | 22/43 | ENST00000306749.4 | |
FASN | XM_011523538.3 | c.3682C>T | p.Leu1228= | synonymous_variant | 22/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.3682C>T | p.Leu1228= | synonymous_variant | 22/43 | 1 | NM_004104.5 | P1 | |
FASN | ENST00000634990.1 | c.3682C>T | p.Leu1228= | synonymous_variant | 22/43 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00918 AC: 1397AN: 152240Hom.: 21 Cov.: 33
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GnomAD3 exomes AF: 0.00242 AC: 550AN: 227150Hom.: 5 AF XY: 0.00184 AC XY: 229AN XY: 124400
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GnomAD4 exome AF: 0.000981 AC: 1419AN: 1446132Hom.: 31 Cov.: 39 AF XY: 0.000856 AC XY: 616AN XY: 719208
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GnomAD4 genome AF: 0.00918 AC: 1398AN: 152358Hom.: 21 Cov.: 33 AF XY: 0.00864 AC XY: 644AN XY: 74504
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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 | Jun 14, 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 27, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at