Genetic Variant FOSL1:p.Gln77Gln (chr11-65896875-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005438.5(FOSL1):c.231A>G(p.Gln77Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,612,732 control chromosomes in the GnomAD database, including 185,014 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 0.50 ( 19751 hom., cov: 31)

Exomes 𝑓: 0.47 ( 165263 hom. )

Consequence

FOSL1
NM_005438.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0850

Publications

31 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP7

Synonymous conserved (PhyloP=-0.085 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOSL1	NM_005438.5 link	c.231A>G	p.Gln77Gln	synonymous_variant	Exon 2 of 4	ENST00000312562.7	NP_005429.1	P15407-1A0A0S2Z595

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOSL1	ENST00000312562.7 link	c.231A>G	p.Gln77Gln	synonymous_variant	Exon 2 of 4	1	NM_005438.5	ENSP00000310170.2		P15407-1

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76063

AN:

151668

Hom.:

19716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.566

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.606

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.499

GnomAD2 exomes

AF:

0.514

AC:

128891

AN:

250844

AF XY:

0.501

show subpopulations

Gnomad AFR exome

AF:

0.564

Gnomad AMR exome

AF:

0.707

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.765

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.444

Gnomad OTH exome

AF:

0.490

GnomAD4 exome

AF:

0.469

AC:

685813

AN:

1460944

Hom.:

165263

Cov.:

AF XY:

0.468

AC XY:

339956

AN XY:

726816

show subpopulations

African (AFR)

AF:

0.568

AC:

19027

AN:

33470

American (AMR)

AF:

0.698

AC:

31196

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

12842

AN:

26122

East Asian (EAS)

AF:

0.774

AC:

30725

AN:

39698

South Asian (SAS)

AF:

0.476

AC:

41012

AN:

86226

European-Finnish (FIN)

AF:

0.400

AC:

21346

AN:

53400

Middle Eastern (MID)

AF:

0.423

AC:

2437

AN:

5758

European-Non Finnish (NFE)

AF:

0.448

AC:

498047

AN:

1111204

Other (OTH)

AF:

0.483

AC:

29181

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

17091

34183

51274

68366

85457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15268

30536

45804

61072

76340

<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:

0.502

AC:

76160

AN:

151788

Hom.:

19751

Cov.:

AF XY:

0.503

AC XY:

37341

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.566

AC:

23407

AN:

41362

American (AMR)

AF:

0.607

AC:

9257

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1694

AN:

3468

East Asian (EAS)

AF:

0.761

AC:

3924

AN:

5154

South Asian (SAS)

AF:

0.490

AC:

2355

AN:

4810

European-Finnish (FIN)

AF:

0.381

AC:

4011

AN:

10520

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.440

AC:

29906

AN:

67912

Other (OTH)

AF:

0.501

AC:

1054

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1944

3889

5833

7778

9722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.466

Hom.:

7493

Bravo

AF:

0.527

Asia WGS

AF:

0.605

AC:

2104

AN:

3478

EpiCase

AF:

0.438

EpiControl

AF:

0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.9

(source)

DANN

Benign

0.74

PhyloP100

-0.085

Mutation Taster

=100/0

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