rs1304050057

Variant names:

• chr11-65896912-G-A
• rs1304050057
• NM_005438.5:c.194C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-65896912-G-A
• chr11-65896912-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The NM_005438.5(FOSL1):​c.194C>T​(p.Pro65Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: FOSL1 NM_005438.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31170958).
• BS2: High AC in GnomAdExome4 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.194C>T	p.Pro65Leu	missense	Exon 2 of 4	NP_005429.1	A0A0S2Z595
	FOSL1	NM_001300844.2		c.194C>T	p.Pro65Leu	missense	Exon 2 of 3	NP_001287773.1	E9PPX2
	FOSL1	NM_001300855.2		c.194C>T	p.Pro65Leu	missense	Exon 2 of 4	NP_001287784.1	E9PKL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL1	ENST00000312562.7	TSL:1 MANE Select	c.194C>T	p.Pro65Leu	missense	Exon 2 of 4	ENSP00000310170.2	P15407-1
	FOSL1	ENST00000531493.5	TSL:1	c.194C>T	p.Pro65Leu	missense	Exon 2 of 3	ENSP00000436276.1	E9PPX2
	FOSL1	ENST00000913992.1		c.191C>T	p.Pro64Leu	missense	Exon 2 of 4	ENSP00000584051.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251390 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461664 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727158

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000894 AC: 4 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111822

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.13
BayesDel_addAF	Benign	0.0037	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.4
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.65	P
Vest4		0.21
MutPred		0.34		Gain of catalytic residue at P65 (P = 0.0204)
MVP		0.84
MPC		0.40
ClinPred		0.92	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.15
gMVP		0.65
Mutation Taster		=74/26	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: rs1304050057; hg19: chr11-65664383;