rs573497934
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_004104.5(FASN):c.4123-10G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,607,592 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 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
FASN
NM_004104.5 splice_polypyrimidine_tract, intron
NM_004104.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00001123
2
Clinical Significance
Conservation
PhyloP100: -1.19
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 17-82085412-C-A is Benign according to our data. Variant chr17-82085412-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 753885.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FASN | NM_004104.5 | c.4123-10G>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000306749.4 | |||
FASN | XM_011523538.3 | c.4123-10G>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FASN | ENST00000306749.4 | c.4123-10G>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004104.5 | P1 | |||
FASN | ENST00000634990.1 | c.4117-10G>T | splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
FASN | ENST00000579410.1 | n.180-10G>T | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 34
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1455408Hom.: 0 Cov.: 70 AF XY: 0.00000138 AC XY: 1AN XY: 723620
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74334
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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 submitter | clinical testing | Invitae | Sep 21, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
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Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at