11-65896873-G-T

Variant names:

• chr11-65896873-G-T
• NM_005438.5:c.233C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005438.5(FOSL1):​c.233C>A​(p.Pro78His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: FOSL1 NM_005438.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23010543).

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.233C>A	p.Pro78His	missense	Exon 2 of 4	NP_005429.1	A0A0S2Z595
	FOSL1	NM_001300844.2		c.233C>A	p.Pro78His	missense	Exon 2 of 3	NP_001287773.1	E9PPX2
	FOSL1	NM_001300855.2		c.233C>A	p.Pro78His	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.233C>A	p.Pro78His	missense	Exon 2 of 4	ENSP00000310170.2	P15407-1
	FOSL1	ENST00000531493.5	TSL:1	c.233C>A	p.Pro78His	missense	Exon 2 of 3	ENSP00000436276.1	E9PPX2
	FOSL1	ENST00000913992.1		c.230C>A	p.Pro77His	missense	Exon 2 of 4	ENSP00000584051.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	0.0055	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.48	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.17
MutPred		0.23		Gain of sheet (P = 0.0085)
MVP		0.84
MPC		0.11
ClinPred		0.44	T
GERP RS		4.1
Varity_R		0.12
gMVP		0.55
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr11-65664344;