rs28381252

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006732.3(FOSB):c.*234T>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 0.00244 in 485,236 control chromosomes in the GnomAD database, including 21 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 0.0015 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 13 hom. )

Consequence

FOSB
NM_006732.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00700

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00152 (228/149924) while in subpopulation EAS AF = 0.038 (189/4980). AF 95% confidence interval is 0.0335. There are 8 homozygotes in GnomAd4. There are 131 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 228 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FOSB	NM_006732.3 link	c.*234T>C	3_prime_UTR_variant	Exon 4 of 4	ENST00000353609.8	NP_006723.2
FOSB	NM_001114171.2 link	c.*234T>C	3_prime_UTR_variant	Exon 3 of 3		NP_001107643.1
FOSB	NM_001411069.1 link	c.*397T>C	3_prime_UTR_variant	Exon 5 of 5		NP_001397998.1
FOSB	XM_047438550.1 link	c.*397T>C	3_prime_UTR_variant	Exon 4 of 4		XP_047294506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOSB	ENST00000353609.8 link	c.*234T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_006732.3	ENSP00000245919.3

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

229

AN:

149808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000464

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0383

Gnomad SAS

AF:

0.00321

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000446

Gnomad OTH

AF:

0.00243

GnomAD4 exome

AF:

0.00285

AC:

957

AN:

335312

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

487

AN XY:

177438

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

9112

American (AMR)

AF:

0.00

AC:

AN:

12436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10192

East Asian (EAS)

AF:

0.0399

AC:

837

AN:

20988

South Asian (SAS)

AF:

0.000956

AC:

AN:

37674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20656

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1464

European-Non Finnish (NFE)

AF:

0.0000344

AC:

AN:

203556

Other (OTH)

AF:

0.00385

AC:

AN:

19234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

118

158

197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00152

AC:

228

AN:

149924

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

131

AN XY:

73186

show subpopulations

African (AFR)

AF:

0.000195

AC:

AN:

41050

American (AMR)

AF:

0.000463

AC:

AN:

15122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3422

East Asian (EAS)

AF:

0.0380

AC:

189

AN:

4980

South Asian (SAS)

AF:

0.00321

AC:

AN:

4674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000446

AC:

AN:

67318

Other (OTH)

AF:

0.00288

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000630

Hom.:

Bravo

AF:

0.00141

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

-0.0070

Mutation Taster

=100/0

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