NM_005438.5:c.55G>A

Variant names:

• chr11-65900285-C-T
• rs1408368762
• NM_005438.5:c.55G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005438.5(FOSL1):​c.55G>A​(p.Gly19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000474 in 1,244,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: FOSL1 NM_005438.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.968
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18259358).
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005438.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL1	NM_005438.5	MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 1 of 4	NP_005429.1	A0A0S2Z595
	FOSL1	NM_001300844.2		c.55G>A	p.Gly19Ser	missense	Exon 1 of 3	NP_001287773.1	E9PPX2
	FOSL1	NM_001300856.2		c.55G>A	p.Gly19Ser	missense	Exon 1 of 3	NP_001287785.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL1	ENST00000312562.7	TSL:1 MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 1 of 4	ENSP00000310170.2	P15407-1
	FOSL1	ENST00000531493.5	TSL:1	c.55G>A	p.Gly19Ser	missense	Exon 1 of 3	ENSP00000436276.1	E9PPX2
	FOSL1	ENST00000913992.1		c.55G>A	p.Gly19Ser	missense	Exon 1 of 4	ENSP00000584051.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000494 AC: 54 AN: 1092714 Hom.: 0 Cov.: 30 AF XY: 0.0000597 AC XY: 31 AN XY: 519054

African (AFR) AF: 0.00 AC: 0 AN: 23010

American (AMR) AF: 0.00 AC: 0 AN: 8518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14526

East Asian (EAS) AF: 0.00 AC: 0 AN: 26670

South Asian (SAS) AF: 0.00 AC: 0 AN: 24576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3056

European-Non Finnish (NFE) AF: 0.0000550 AC: 51 AN: 926600

Other (OTH) AF: 0.0000682 AC: 3 AN: 43986

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.0087	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.0021
Eigen_PC	Benign	-0.065
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.97
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.28
Sift	Benign	0.11	T
Sift4G	Benign	0.44	T
Polyphen		1.0	D
Vest4		0.23
MutPred		0.23		Gain of glycosylation at G19 (P = 0.0012)
MVP		0.77
MPC		0.50
ClinPred		0.63	D
GERP RS		3.5
PromoterAI		-0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.031
gMVP		0.37
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs1408368762; hg19: chr11-65667756;