Genetic Variant FOSL1:p.Phe5Val (chr11-65900327-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005438.5(FOSL1):c.13T>G(p.Phe5Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000741 in 1,240,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

FOSL1
NM_005438.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

Publications

0 publications found

Variant links:

Genes affected

FOSL1 (HGNC:13718): (FOS like 1, 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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

FOSL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18272668).

BS2

High AC in GnomAd4 at 21 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005438.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOSL1	NM_005438.5	MANE Select	c.13T>G	p.Phe5Val	missense	Exon 1 of 4	NP_005429.1	A0A0S2Z595
FOSL1	NM_001300844.2		c.13T>G	p.Phe5Val	missense	Exon 1 of 3	NP_001287773.1	E9PPX2
FOSL1	NM_001300856.2		c.13T>G	p.Phe5Val	missense	Exon 1 of 3	NP_001287785.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOSL1	ENST00000312562.7	TSL:1 MANE Select	c.13T>G	p.Phe5Val	missense	Exon 1 of 4	ENSP00000310170.2	P15407-1
FOSL1	ENST00000531493.5	TSL:1	c.13T>G	p.Phe5Val	missense	Exon 1 of 3	ENSP00000436276.1	E9PPX2
FOSL1	ENST00000913992.1		c.13T>G	p.Phe5Val	missense	Exon 1 of 4	ENSP00000584051.1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00

AC:

AN:

1952

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000652

AC:

AN:

1088756

Hom.:

Cov.:

AF XY:

0.0000600

AC XY:

AN XY:

516286

show subpopulations

African (AFR)

AF:

0.0000435

AC:

AN:

22990

American (AMR)

AF:

0.00

AC:

AN:

8432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14424

East Asian (EAS)

AF:

0.00

AC:

AN:

26630

South Asian (SAS)

AF:

0.00

AC:

AN:

23050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3620

European-Non Finnish (NFE)

AF:

0.0000725

AC:

AN:

924178

Other (OTH)

AF:

0.0000683

AC:

AN:

43904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000138

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41446

American (AMR)

AF:

0.000131

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68010

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000285

Hom.:

Bravo

AF:

0.000125

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.13

Eigen_PC

Benign

0.033

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.40

M_CAP

Benign

0.061

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.1

PhyloP100

4.7

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.040

REVEL

Uncertain

0.30

Sift

Benign

0.28

Sift4G

Uncertain

0.012

Polyphen

0.010

Vest4

0.35

MutPred

0.26

Gain of relative solvent accessibility (P = 0.1012)

MVP

0.80

MPC

0.14

ClinPred

0.92

GERP RS

4.4

PromoterAI

0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.16

gMVP

0.56

Mutation Taster

=82/18

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over