rs780193148
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006732.3(FOSB):āc.220A>Cā(p.Thr74Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,540 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
FOSB
NM_006732.3 missense
NM_006732.3 missense
Scores
5
11
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.50
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 Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FOSB | NM_006732.3 | c.220A>C | p.Thr74Pro | missense_variant | Exon 2 of 4 | ENST00000353609.8 | NP_006723.2 | |
FOSB | NM_001114171.2 | c.220A>C | p.Thr74Pro | missense_variant | Exon 2 of 3 | NP_001107643.1 | ||
FOSB | NM_001411069.1 | c.220A>C | p.Thr74Pro | missense_variant | Exon 2 of 5 | NP_001397998.1 | ||
FOSB | XM_047438550.1 | c.220A>C | p.Thr74Pro | missense_variant | Exon 2 of 4 | XP_047294506.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460540Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726682
GnomAD4 exome
AF:
AC:
7
AN:
1460540
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Cov.:
31
AF XY:
AC XY:
4
AN XY:
726682
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
AF:
AC:
7
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;.;D;.;T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;T;T;T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
M;M;M;.;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;D;.;.;.;.;.
REVEL
Uncertain
Sift
Uncertain
.;D;D;.;.;.;.;.
Sift4G
Uncertain
D;D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at P73 (P = 0.0112);Gain of catalytic residue at P73 (P = 0.0112);Gain of catalytic residue at P73 (P = 0.0112);Gain of catalytic residue at P73 (P = 0.0112);Gain of catalytic residue at P73 (P = 0.0112);.;.;.;
MVP
MPC
1.6
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at