rs12473028

Positions:

• chr2-28395294-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005253.4(FOSL2):​c.102+1472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,124 control chromosomes in the GnomAD database, including 11,795 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 0.39 (11795 hom., cov: 32)
• Consequence: FOSL2 NM_005253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOSL2	NM_005253.4	c.102+1472G>A		intron_variant		ENST00000264716.9
FOSL2	XM_005264231.5	c.102+1472G>A		intron_variant
FOSL2	XM_006711976.4	c.102+1472G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOSL2	ENST00000264716.9	c.102+1472G>A		intron_variant		1	NM_005253.4	P1
FOSL2	ENST00000379619.5	c.27+2458G>A		intron_variant		1
FOSL2	ENST00000460736.1	n.97+2750G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59335 AN: 152006 Hom.: 11783 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.390 AC: 59388 AN: 152124 Hom.: 11795 Cov.: 32 AF XY: 0.388 AC XY: 28876 AN XY: 74378

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.364

Alfa AF: 0.396 Hom.: 12038

Bravo AF: 0.382

Asia WGS AF: 0.339 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs12473028; hg19: chr2-28618161;