Variant 19-45468703-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_006732.3(FOSB):c.117C>G(p.Ala39Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,602,910 control chromosomes in the GnomAD database, including 94,061 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 0.38 ( 12426 hom., cov: 31)

Exomes 𝑓: 0.33 ( 81635 hom. )

Consequence

FOSB
NM_006732.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

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]

FOSB links:

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]

ERCC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP7

Synonymous conserved (PhyloP=1.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOSB	NM_006732.3 linkuse as main transcript	c.117C>G	p.Ala39Ala	synonymous_variant	1/4	ENST00000353609.8	NP_006723.2	P53539-1A0A024R0P6
FOSB	NM_001114171.2 linkuse as main transcript	c.117C>G	p.Ala39Ala	synonymous_variant	1/3		NP_001107643.1	P53539-2
FOSB	NM_001411069.1 linkuse as main transcript	c.117C>G	p.Ala39Ala	synonymous_variant	1/5		NP_001397998.1
FOSB	XM_047438550.1 linkuse as main transcript	c.117C>G	p.Ala39Ala	synonymous_variant	1/4		XP_047294506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOSB	ENST00000353609.8 linkuse as main transcript	c.117C>G	p.Ala39Ala	synonymous_variant	1/4	1	NM_006732.3	ENSP00000245919.3		P53539-1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58287

AN:

151766

Hom.:

12401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.366

GnomAD3 exomes

AF:

0.328

AC:

78405

AN:

239208

Hom.:

14141

AF XY:

0.334

AC XY:

43479

AN XY:

130372

show subpopulations

Gnomad AFR exome

AF:

0.575

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.236

Gnomad SAS exome

AF:

0.431

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.330

AC:

478736

AN:

1451026

Hom.:

81635

Cov.:

AF XY:

0.333

AC XY:

240203

AN XY:

722084

show subpopulations

Gnomad4 AFR exome

AF:

0.579

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.269

Gnomad4 EAS exome

AF:

0.283

Gnomad4 SAS exome

AF:

0.423

Gnomad4 FIN exome

AF:

0.355

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.384

AC:

58343

AN:

151884

Hom.:

12426

Cov.:

AF XY:

0.381

AC XY:

28255

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.570

Gnomad4 AMR

AF:

0.247

Gnomad4 ASJ

AF:

0.258

Gnomad4 EAS

AF:

0.238

Gnomad4 SAS

AF:

0.421

Gnomad4 FIN

AF:

0.343

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.334

Hom.:

2904

Bravo

AF:

0.378

Asia WGS

AF:

0.327

AC:

1140

AN:

3478

EpiCase

AF:

0.328

EpiControl

AF:

0.327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.79

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over