rs637571

Positions:

• chr11-65896875-T-A
• chr11-65896875-T-C
• chr11-65896875-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000312562.7(FOSL1):​c.231A>T​(p.Gln77His) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FOSL1 ENST00000312562.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34962496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOSL1	NM_005438.5	c.231A>T	p.Gln77His	missense_variant	2/4	ENST00000312562.7	NP_005429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOSL1	ENST00000312562.7	c.231A>T	p.Gln77His	missense_variant	2/4	1	NM_005438.5	ENSP00000310170	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;.;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	0.51	P;P;P;P;P
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.23	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.51	T;T;D
Sift4G	Benign	0.56	T;T;T
Polyphen		0.99	D;.;.
Vest4		0.30
MutPred		0.16		Gain of methylation at R79 (P = 0.0437);Gain of methylation at R79 (P = 0.0437);Gain of methylation at R79 (P = 0.0437);
MVP		0.72
MPC		0.26
ClinPred		0.59	D
GERP RS		2.0
Varity_R		0.048
gMVP		0.46

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: rs637571; hg19: chr11-65664346;