NM_005438.5:c.100-779T>C

Variant names:

• chr11-65897785-A-G
• rs634534
• NM_005438.5:c.100-779T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005438.5(FOSL1):​c.100-779T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,992 control chromosomes in the GnomAD database, including 15,627 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (15627 hom., cov: 30)
• Consequence: FOSL1 NM_005438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL1	NM_005438.5	MANE Select	c.100-779T>C		intron	N/A	NP_005429.1
	FOSL1	NM_001300844.2		c.100-779T>C		intron	N/A	NP_001287773.1
	FOSL1	NM_001300856.2		c.99+2456T>C		intron	N/A	NP_001287785.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL1	ENST00000312562.7	TSL:1 MANE Select	c.100-779T>C		intron	N/A	ENSP00000310170.2
	FOSL1	ENST00000531493.5	TSL:1	c.100-779T>C		intron	N/A	ENSP00000436276.1
	FOSL1	ENST00000448083.6	TSL:2	c.99+2456T>C		intron	N/A	ENSP00000393302.2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63456 AN: 151880 Hom.: 15635 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.447

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.417 AC: 63433 AN: 151992 Hom.: 15627 Cov.: 30 AF XY: 0.420 AC XY: 31211 AN XY: 74288

African (AFR) AF: 0.166 AC: 6894 AN: 41474

American (AMR) AF: 0.359 AC: 5473 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1856 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1281 AN: 5174

South Asian (SAS) AF: 0.522 AC: 2517 AN: 4824

European-Finnish (FIN) AF: 0.616 AC: 6485 AN: 10528

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37355 AN: 67950

Other (OTH) AF: 0.445 AC: 935 AN: 2102

Alfa AF: 0.506 Hom.: 9598

Bravo AF: 0.382

Asia WGS AF: 0.377 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.73
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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: rs634534; hg19: chr11-65665256;