rs28381252
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_006732.3(FOSB):c.*234T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 485,236 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0015 ( 8 hom., cov: 31)
Exomes 𝑓: 0.0029 ( 13 hom. )
Consequence
FOSB
NM_006732.3 3_prime_UTR
NM_006732.3 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.00700
Genes affected
FOSB (HGNC:3797): (FosB proto-oncogene, AP-1 transcription factor subunit) The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
ERCC1 (HGNC:3433): (ERCC excision repair 1, endonuclease non-catalytic subunit) The product of this gene functions in the nucleotide excision repair pathway, and is required for the repair of DNA lesions such as those induced by UV light or formed by electrophilic compounds including cisplatin. The encoded protein forms a heterodimer with the XPF endonuclease (also known as ERCC4), and the heterodimeric endonuclease catalyzes the 5' incision in the process of excising the DNA lesion. The heterodimeric endonuclease is also involved in recombinational DNA repair and in the repair of inter-strand crosslinks. Mutations in this gene result in cerebrooculofacioskeletal syndrome, and polymorphisms that alter expression of this gene may play a role in carcinogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. The last exon of this gene overlaps with the CD3e molecule, epsilon associated protein gene on the opposite strand. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00152 (228/149924) while in subpopulation EAS AF= 0.038 (189/4980). AF 95% confidence interval is 0.0335. There are 8 homozygotes in gnomad4. There are 131 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 228 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FOSB | NM_006732.3 | c.*234T>C | 3_prime_UTR_variant | 4/4 | ENST00000353609.8 | NP_006723.2 | ||
FOSB | NM_001114171.2 | c.*234T>C | 3_prime_UTR_variant | 3/3 | NP_001107643.1 | |||
FOSB | NM_001411069.1 | c.*397T>C | 3_prime_UTR_variant | 5/5 | NP_001397998.1 | |||
FOSB | XM_047438550.1 | c.*397T>C | 3_prime_UTR_variant | 4/4 | XP_047294506.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FOSB | ENST00000353609.8 | c.*234T>C | 3_prime_UTR_variant | 4/4 | 1 | NM_006732.3 | ENSP00000245919.3 |
Frequencies
GnomAD3 genomes AF: 0.00153 AC: 229AN: 149808Hom.: 8 Cov.: 31
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GnomAD4 exome AF: 0.00285 AC: 957AN: 335312Hom.: 13 Cov.: 4 AF XY: 0.00274 AC XY: 487AN XY: 177438
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GnomAD4 genome AF: 0.00152 AC: 228AN: 149924Hom.: 8 Cov.: 31 AF XY: 0.00179 AC XY: 131AN XY: 73186
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ClinVar
Not reported inComputational 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