rs141976219

Variant names:

• chr11-65893019-G-C
• rs141976219
• NM_005438.5:c.683C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-65893019-G-C
• chr11-65893019-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005438.5(FOSL1):​c.683C>G​(p.Pro228Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P228H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOSL1 NM_005438.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.62

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOSL1	NM_005438.5	c.683C>G	p.Pro228Arg	missense_variant	Exon 4 of 4	ENST00000312562.7	NP_005429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOSL1	ENST00000312562.7	c.683C>G	p.Pro228Arg	missense_variant	Exon 4 of 4	1	NM_005438.5	ENSP00000310170.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	.;D;.;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;.
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	2.0	.;M;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D;D;D;.
Sift4G	Uncertain	0.0040	D;D;D;.
Polyphen		0.99	.;D;.;.
Vest4		0.51
MutPred		0.23		.;Gain of solvent accessibility (P = 0.008);.;.;
MVP		0.88
MPC		0.50
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.50
gMVP		0.54

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: rs141976219; hg19: chr11-65660490;