19-45471335-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000590335.1(FOSB):​c.*299T>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 0.489 in 1,442,792 control chromosomes in the GnomAD database, including 176,662 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 0.54 ( 22959 hom., cov: 31)
Exomes 𝑓: 0.48 ( 153703 hom. )

Consequence

FOSB
ENST00000590335.1 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.23
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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOSBNM_006732.3 linkc.555+34T>C intron_variant Intron 3 of 3 ENST00000353609.8 NP_006723.2 P53539-1A0A024R0P6
FOSBNM_001114171.2 linkc.447+386T>C intron_variant Intron 2 of 2 NP_001107643.1 P53539-2
FOSBNM_001411069.1 linkc.555+34T>C intron_variant Intron 3 of 4 NP_001397998.1
FOSBXM_047438550.1 linkc.447+386T>C intron_variant Intron 2 of 3 XP_047294506.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOSBENST00000353609.8 linkc.555+34T>C intron_variant Intron 3 of 3 1 NM_006732.3 ENSP00000245919.3 P53539-1

Frequencies

GnomAD3 genomes
AF:
0.539
AC:
81763
AN:
151674
Hom.:
22926
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.692
Gnomad AMI
AF:
0.434
Gnomad AMR
AF:
0.508
Gnomad ASJ
AF:
0.437
Gnomad EAS
AF:
0.644
Gnomad SAS
AF:
0.676
Gnomad FIN
AF:
0.439
Gnomad MID
AF:
0.503
Gnomad NFE
AF:
0.458
Gnomad OTH
AF:
0.533
GnomAD3 exomes
AF:
0.527
AC:
80542
AN:
152874
Hom.:
22006
AF XY:
0.532
AC XY:
43012
AN XY:
80904
show subpopulations
Gnomad AFR exome
AF:
0.701
Gnomad AMR exome
AF:
0.524
Gnomad ASJ exome
AF:
0.444
Gnomad EAS exome
AF:
0.639
Gnomad SAS exome
AF:
0.672
Gnomad FIN exome
AF:
0.439
Gnomad NFE exome
AF:
0.460
Gnomad OTH exome
AF:
0.504
GnomAD4 exome
AF:
0.483
AC:
623647
AN:
1291000
Hom.:
153703
Cov.:
19
AF XY:
0.488
AC XY:
312954
AN XY:
641100
show subpopulations
Gnomad4 AFR exome
AF:
0.696
Gnomad4 AMR exome
AF:
0.520
Gnomad4 ASJ exome
AF:
0.441
Gnomad4 EAS exome
AF:
0.633
Gnomad4 SAS exome
AF:
0.669
Gnomad4 FIN exome
AF:
0.443
Gnomad4 NFE exome
AF:
0.457
Gnomad4 OTH exome
AF:
0.510
GnomAD4 genome
AF:
0.539
AC:
81843
AN:
151792
Hom.:
22959
Cov.:
31
AF XY:
0.542
AC XY:
40188
AN XY:
74182
show subpopulations
Gnomad4 AFR
AF:
0.693
Gnomad4 AMR
AF:
0.508
Gnomad4 ASJ
AF:
0.437
Gnomad4 EAS
AF:
0.643
Gnomad4 SAS
AF:
0.675
Gnomad4 FIN
AF:
0.439
Gnomad4 NFE
AF:
0.458
Gnomad4 OTH
AF:
0.534
Alfa
AF:
0.480
Hom.:
26771
Bravo
AF:
0.549
Asia WGS
AF:
0.654
AC:
2276
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.91
DANN
Benign
0.75

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: rs2276469; hg19: chr19-45974593; COSMIC: COSV62278461; API