Variant chr14-75280809-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005252.4(FOS):c.528G>C(p.Lys176Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00542 in 1,614,080 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 38 hom. )

Consequence

FOS
NM_005252.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

FOS (HGNC:3796): (Fos 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. In some cases, expression of the FOS gene has also been associated with apoptotic cell death. [provided by RefSeq, Jul 2008]

FOS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009449899).

BP6

Variant 14-75280809-G-C is Benign according to our data. Variant chr14-75280809-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 710469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 732 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOS	NM_005252.4 linkuse as main transcript	c.528G>C	p.Lys176Asn	missense_variant	4/4	ENST00000303562.9	NP_005243.1	P01100-1Q6FG41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOS	ENST00000303562.9 linkuse as main transcript	c.528G>C	p.Lys176Asn	missense_variant	4/4	1	NM_005252.4	ENSP00000306245.4		P01100-1

Frequencies

GnomAD3 genomes

AF:

0.00481

AC:

732

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0223

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00591

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00468

AC:

1173

AN:

250786

Hom.:

AF XY:

0.00465

AC XY:

632

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.000937

Gnomad AMR exome

AF:

0.00197

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.0201

Gnomad NFE exome

AF:

0.00526

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00549

AC:

8019

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00527

AC XY:

3835

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000962

Gnomad4 FIN exome

AF:

0.0190

Gnomad4 NFE exome

AF:

0.00585

Gnomad4 OTH exome

AF:

0.00447

GnomAD4 genome

AF:

0.00481

AC:

732

AN:

152242

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0223

Gnomad4 NFE

AF:

0.00591

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00335

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.00457

AC:

555

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00433

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	FOS: BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;.;.;T;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

D;D;D;D;D

MetaRNN

Benign

0.0094

T;T;T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.77

N;.;.;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-4.4

D;D;D;D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D

Polyphen

1.0

D;.;.;.;.

Vest4

0.58

MutPred

0.41

Loss of ubiquitination at K176 (P = 0.0012);.;.;.;.;

MVP

0.91

MPC

2.3

ClinPred

0.034

GERP RS

4.5

Varity_R

0.93

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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