chr11-65900309-T-C

Variant names:

• chr11-65900309-T-C
• rs1479161684
• NM_005438.5:c.31A>G

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.31A>G​(p.Ser11Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,091,714 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: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: FOSL1 NM_005438.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.253
• Publications: 1 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=0.14858934).

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.31A>G	p.Ser11Gly	missense	Exon 1 of 4	NP_005429.1	A0A0S2Z595
	FOSL1	NM_001300844.2		c.31A>G	p.Ser11Gly	missense	Exon 1 of 3	NP_001287773.1	E9PPX2
	FOSL1	NM_001300856.2		c.31A>G	p.Ser11Gly	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.31A>G	p.Ser11Gly	missense	Exon 1 of 4	ENSP00000310170.2	P15407-1
	FOSL1	ENST00000531493.5	TSL:1	c.31A>G	p.Ser11Gly	missense	Exon 1 of 3	ENSP00000436276.1	E9PPX2
	FOSL1	ENST00000913992.1		c.31A>G	p.Ser11Gly	missense	Exon 1 of 4	ENSP00000584051.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000366 AC: 4 AN: 1091714 Hom.: 0 Cov.: 30 AF XY: 0.00000386 AC XY: 2 AN XY: 518304

African (AFR) AF: 0.00 AC: 0 AN: 23008

American (AMR) AF: 0.00 AC: 0 AN: 8494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14492

East Asian (EAS) AF: 0.000112 AC: 3 AN: 26668

South Asian (SAS) AF: 0.00 AC: 0 AN: 23988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 926132

Other (OTH) AF: 0.0000227 AC: 1 AN: 43962

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.084
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.068
Eigen_PC	Benign	0.017
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.25
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.39
Sift	Benign	0.11	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.78	P
Vest4		0.23
MutPred		0.14		Loss of phosphorylation at S11 (P = 0.0147)
MVP		0.72
MPC		0.42
ClinPred		0.72	D
GERP RS		4.4
PromoterAI		-0.018	Neutral
Varity_R		0.13
gMVP		0.29
Mutation Taster		=85/15	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: rs1479161684; hg19: chr11-65667780; COSMIC: COSV57027763;