chr19-45468683-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_006732.3(FOSB):c.97G>A(p.Gly33Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000878 in 1,611,072 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.0048 ( 2 hom., cov: 31)
Exomes 𝑓: 0.00047 ( 8 hom. )
Consequence
FOSB
NM_006732.3 missense
NM_006732.3 missense
Scores
6
8
Clinical Significance
Conservation
PhyloP100: 3.77
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0075651407).
BP6
Variant 19-45468683-G-A is Benign according to our data. Variant chr19-45468683-G-A is described in ClinVar as [Benign]. Clinvar id is 785628.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00475 (723/152124) while in subpopulation AFR AF= 0.0168 (698/41498). AF 95% confidence interval is 0.0158. There are 2 homozygotes in gnomad4. There are 333 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 723 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOSB | NM_006732.3 | c.97G>A | p.Gly33Ser | missense_variant | 1/4 | ENST00000353609.8 | |
FOSB | NM_001114171.2 | c.97G>A | p.Gly33Ser | missense_variant | 1/3 | ||
FOSB | NM_001411069.1 | c.97G>A | p.Gly33Ser | missense_variant | 1/5 | ||
FOSB | XM_047438550.1 | c.97G>A | p.Gly33Ser | missense_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOSB | ENST00000353609.8 | c.97G>A | p.Gly33Ser | missense_variant | 1/4 | 1 | NM_006732.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00472 AC: 718AN: 152008Hom.: 2 Cov.: 31
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GnomAD3 exomes AF: 0.00123 AC: 303AN: 246716Hom.: 3 AF XY: 0.000947 AC XY: 127AN XY: 134038
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GnomAD4 exome AF: 0.000474 AC: 691AN: 1458948Hom.: 8 Cov.: 30 AF XY: 0.000416 AC XY: 302AN XY: 725850
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GnomAD4 genome AF: 0.00475 AC: 723AN: 152124Hom.: 2 Cov.: 31 AF XY: 0.00448 AC XY: 333AN XY: 74358
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;L;L;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
1.0
.;.;.;D;.;.;.;.
Vest4
MVP
MPC
1.7
ClinPred
T
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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