Variant 11-65893129-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005438.5(FOSL1):c.573C>A(p.Ser191Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 1,612,984 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 4 hom. )

Consequence

FOSL1
NM_005438.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.19

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063978434).

BP6

Variant 11-65893129-G-T is Benign according to our data. Variant chr11-65893129-G-T is described in ClinVar as [Benign]. Clinvar id is 710011.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 567 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOSL1	NM_005438.5 linkuse as main transcript	c.573C>A	p.Ser191Arg	missense_variant	4/4	ENST00000312562.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOSL1	ENST00000312562.7 linkuse as main transcript	c.573C>A	p.Ser191Arg	missense_variant	4/4	1	NM_005438.5	P1	P15407-1

Frequencies

GnomAD3 genomes

AF:

0.00372

AC:

566

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

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:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000997

AC:

249

AN:

249844

Hom.:

AF XY:

0.000710

AC XY:

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.000930

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000391

AC:

571

AN:

1460746

Hom.:

Cov.:

AF XY:

0.000340

AC XY:

247

AN XY:

726642

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.00372

AC:

567

AN:

152238

Hom.:

Cov.:

AF XY:

0.00369

AC XY:

275

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000655

Hom.:

Bravo

AF:

0.00427

ESP6500AA

AF:

0.0120

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00105

AC:

127

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

.;T;.

Eigen

Benign

0.096

Eigen_PC

Benign

0.080

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

T;T;T

MetaRNN

Benign

0.0064

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.90

.;L;.

MutationTaster

Benign

0.87

D;D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.99

.;D;.

Vest4

0.12

MutPred

0.31

.;Gain of solvent accessibility (P = 0.0014);.;

MVP

0.80

MPC

0.44

ClinPred

0.051

GERP RS

3.6

Varity_R

0.088

gMVP

0.48

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over