Variant 14-75280102-A-G 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_005252.4(FOS):c.367A>G(p.Ile123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,613,986 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 6 hom. )

Consequence

FOS
NM_005252.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.32

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071657896).

BP6

Variant 14-75280102-A-G is Benign according to our data. Variant chr14-75280102-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 770618.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 220 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOS	NM_005252.4 linkuse as main transcript	c.367A>G	p.Ile123Val	missense_variant	2/4	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.367A>G	p.Ile123Val	missense_variant	2/4	1	NM_005252.4	ENSP00000306245.4		P01100-1

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

221

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00174

AC:

434

AN:

249206

Hom.:

AF XY:

0.00166

AC XY:

225

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.000255

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00283

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00218

AC:

3187

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1507

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.000714

Gnomad4 NFE exome

AF:

0.00259

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00144

AC:

220

AN:

152310

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00238

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.00152

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00182

AC:

221

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00245

EpiControl

AF:

0.00273

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely 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

Benign

0.066

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.76

Eigen

Benign

-0.068

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.23

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0072

T;T

MetaSVM

Benign

-0.99

PROVEAN

Benign

1.3

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.17

T;T

Sift4G

Benign

0.48

T;T

MVP

0.93

ClinPred

0.057

GERP RS

6.0

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