19-45468703-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

cerebrooculofacioskeletal syndrome 4
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
Cockayne syndrome type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
COFS syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ERCC1 links:

ENSG00000299344 (HGNC:):

ENSG00000299344 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FOSB	NM_006732.3 link	c.117C>G	p.Ala39Ala	synonymous_variant	Exon 1 of 4	ENST00000353609.8	NP_006723.2	P53539-1A0A024R0P6
FOSB	NM_001114171.2 link	c.117C>G	p.Ala39Ala	synonymous_variant	Exon 1 of 3		NP_001107643.1	P53539-2
FOSB	NM_001411069.1 link	c.117C>G	p.Ala39Ala	synonymous_variant	Exon 1 of 5		NP_001397998.1
FOSB	XM_047438550.1 link	c.117C>G	p.Ala39Ala	synonymous_variant	Exon 1 of 4		XP_047294506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOSB	ENST00000353609.8 link	c.117C>G	p.Ala39Ala	synonymous_variant	Exon 1 of 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

GnomAD2 exomes

AF:

0.328

AC:

78405

AN:

239208

AF XY:

0.334

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 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

African (AFR)

AF:

0.579

AC:

18889

AN:

32606

American (AMR)

AF:

0.174

AC:

7235

AN:

41532

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

6917

AN:

25740

East Asian (EAS)

AF:

0.283

AC:

11150

AN:

39460

South Asian (SAS)

AF:

0.423

AC:

35851

AN:

84804

European-Finnish (FIN)

AF:

0.355

AC:

18906

AN:

53222

Middle Eastern (MID)

AF:

0.356

AC:

1950

AN:

5484

European-Non Finnish (NFE)

AF:

0.323

AC:

357485

AN:

1108258

Other (OTH)

AF:

0.340

AC:

20353

AN:

59920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

16513

33026

49540

66053

82566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11752

23504

35256

47008

58760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.384

AC:

58343

AN:

151884

Hom.:

12426

Cov.:

AF XY:

0.381

AC XY:

28255

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.570

AC:

23599

AN:

41378

American (AMR)

AF:

0.247

AC:

3769

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

893

AN:

3466

East Asian (EAS)

AF:

0.238

AC:

1227

AN:

5156

South Asian (SAS)

AF:

0.421

AC:

2029

AN:

4818

European-Finnish (FIN)

AF:

0.343

AC:

3624

AN:

10562

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22097

AN:

67936

Other (OTH)

AF:

0.361

AC:

760

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1675

3349

5024

6698

8373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.79

PhyloP100

1.4

PromoterAI

0.092

Neutral

(source)

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over