Genetic Variant FOS:c.-60C>T (chr14-75278923-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_005252.4(FOS):c.-60C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,601,574 control chromosomes in the GnomAD database, including 430,796 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 0.77 ( 45333 hom., cov: 34)

Exomes 𝑓: 0.73 ( 385463 hom. )

Consequence

FOS
NM_005252.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.415

Publications

45 publications found

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 Gene-Disease associations (from GenCC):

Berardinelli-Seip congenital lipodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FOS links:

ENSG00000258740 (HGNC:58290):

ENSG00000258740 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOS	NM_005252.4 link	c.-60C>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000303562.9	NP_005243.1	P01100-1Q6FG41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOS	ENST00000303562.9 link	c.-60C>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_005252.4	ENSP00000306245.4		P01100-1

Frequencies

GnomAD3 genomes

AF:

0.766

AC:

116453

AN:

152088

Hom.:

45304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.889

Gnomad AMI

AF:

0.807

Gnomad AMR

AF:

0.665

Gnomad ASJ

AF:

0.683

Gnomad EAS

AF:

0.533

Gnomad SAS

AF:

0.600

Gnomad FIN

AF:

0.794

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.742

GnomAD4 exome

AF:

0.727

AC:

1053426

AN:

1449368

Hom.:

385463

Cov.:

AF XY:

0.723

AC XY:

520791

AN XY:

720668

show subpopulations

African (AFR)

AF:

0.897

AC:

29815

AN:

33244

American (AMR)

AF:

0.664

AC:

28850

AN:

43422

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

17751

AN:

25874

East Asian (EAS)

AF:

0.514

AC:

20137

AN:

39182

South Asian (SAS)

AF:

0.617

AC:

52451

AN:

85066

European-Finnish (FIN)

AF:

0.801

AC:

40370

AN:

50372

Middle Eastern (MID)

AF:

0.740

AC:

4252

AN:

5744

European-Non Finnish (NFE)

AF:

0.738

AC:

816557

AN:

1106614

Other (OTH)

AF:

0.723

AC:

43243

AN:

59850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

14882

29765

44647

59530

74412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20032

40064

60096

80128

100160

<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:

0.766

AC:

116540

AN:

152206

Hom.:

45333

Cov.:

AF XY:

0.761

AC XY:

56656

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.888

AC:

36893

AN:

41536

American (AMR)

AF:

0.665

AC:

10167

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.683

AC:

2369

AN:

3470

East Asian (EAS)

AF:

0.533

AC:

2756

AN:

5168

South Asian (SAS)

AF:

0.601

AC:

2902

AN:

4826

European-Finnish (FIN)

AF:

0.794

AC:

8415

AN:

10596

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.743

AC:

50511

AN:

67996

Other (OTH)

AF:

0.742

AC:

1567

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1397

2794

4192

5589

6986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

850

1700

2550

3400

4250

<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:

0.741

Hom.:

66637

Bravo

AF:

0.763

Asia WGS

AF:

0.592

AC:

2057

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

0.41

PromoterAI

-0.012

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(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