rs780193148

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006732.3(FOSB):ā€‹c.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

Scores

5
11
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.50
Variant links:
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]

Genome browser will be placed here

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
FOSBNM_006732.3 linkc.220A>C p.Thr74Pro missense_variant Exon 2 of 4 ENST00000353609.8 NP_006723.2 P53539-1A0A024R0P6
FOSBNM_001114171.2 linkc.220A>C p.Thr74Pro missense_variant Exon 2 of 3 NP_001107643.1 P53539-2
FOSBNM_001411069.1 linkc.220A>C p.Thr74Pro missense_variant Exon 2 of 5 NP_001397998.1
FOSBXM_047438550.1 linkc.220A>C p.Thr74Pro missense_variant Exon 2 of 4 XP_047294506.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOSBENST00000353609.8 linkc.220A>C p.Thr74Pro missense_variant Exon 2 of 4 1 NM_006732.3 ENSP00000245919.3 P53539-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460540
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
726682
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000115
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000577
AC:
7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.80
.;.;D;.;T;.;.;.
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.78
T;D;T;T;T;T;T;T
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.70
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Benign
2.0
M;M;M;.;.;.;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.7
.;D;D;.;.;.;.;.
REVEL
Uncertain
0.52
Sift
Uncertain
0.015
.;D;D;.;.;.;.;.
Sift4G
Uncertain
0.011
D;D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;.;.;.;.
Vest4
0.66
MutPred
0.48
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
0.55
MPC
1.6
ClinPred
0.99
D
GERP RS
4.8
Varity_R
0.79
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780193148; hg19: chr19-45973980; COSMIC: COSV62278361; COSMIC: COSV62278361; API