Variant chr2-28411923-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005253.4(FOSL2):c.463-7G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,613,402 control chromosomes in the GnomAD database, including 134,510 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 9639 hom., cov: 32)

Exomes 𝑓: 0.41 ( 124871 hom. )

Consequence

FOSL2
NM_005253.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002265

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Variant links:

Genes affected

FOSL2 (HGNC:3798): (FOS like 2, 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. [provided by RefSeq, Jul 2014]

FOSL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FOSL2	NM_005253.4 linkuse as main transcript	c.463-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000264716.9	NP_005244.1
FOSL2	XM_006711976.4 linkuse as main transcript	c.507G>A	p.Pro169=	synonymous_variant	4/4		XP_006712039.1
FOSL2	XM_006711977.4 linkuse as main transcript	c.390G>A	p.Pro130=	synonymous_variant	4/4		XP_006712040.1
FOSL2	XM_005264231.5 linkuse as main transcript	c.566-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_005264288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOSL2	ENST00000379619.5 linkuse as main transcript	c.432G>A	p.Pro144=	synonymous_variant	4/4	1		ENSP00000368939		P15408-2
FOSL2	ENST00000264716.9 linkuse as main transcript	c.463-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005253.4	ENSP00000264716	P1	P15408-1
FOSL2	ENST00000436647.1 linkuse as main transcript	c.346-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000396497

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52385

AN:

152014

Hom.:

9646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.317

GnomAD3 exomes

AF:

0.360

AC:

89691

AN:

249356

Hom.:

17174

AF XY:

0.373

AC XY:

50459

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.283

Gnomad EAS exome

AF:

0.189

Gnomad SAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.411

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.408

AC:

596040

AN:

1461270

Hom.:

124871

Cov.:

AF XY:

0.410

AC XY:

297840

AN XY:

726958

show subpopulations

Gnomad4 AFR exome

AF:

0.234

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.290

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.467

Gnomad4 FIN exome

AF:

0.423

Gnomad4 NFE exome

AF:

0.426

Gnomad4 OTH exome

AF:

0.385

GnomAD4 genome

AF:

0.344

AC:

52386

AN:

152132

Hom.:

9639

Cov.:

AF XY:

0.343

AC XY:

25508

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.245

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.413

Gnomad4 NFE

AF:

0.415

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.384

Hom.:

26828

Bravo

AF:

0.328

Asia WGS

AF:

0.304

AC:

1057

AN:

3478

EpiCase

AF:

0.389

EpiControl

AF:

0.394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.4

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.0020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over