11-65896875-T-C

Position:

• chr11-65896875-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005438.5(FOSL1):​c.231A>G​(p.Gln77Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,612,732 control chromosomes in the GnomAD database, including 185,014 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 0.50 (19751 hom., cov: 31)
  • Exomes 𝑓: 0.47 (165263 hom.)
• Consequence: FOSL1 NM_005438.5 synonymous
• 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]

FOSL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.085 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOSL1	NM_005438.5	c.231A>G	p.Gln77Gln	synonymous_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>G	p.Gln77Gln	synonymous_variant	2/4	1	NM_005438.5	ENSP00000310170.2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76063 AN: 151668 Hom.: 19716 Cov.: 31

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.499

GnomAD3 exomes AF: 0.514 AC: 128891 AN: 250844 Hom.: 34966 AF XY: 0.501 AC XY: 67898 AN XY: 135648

Gnomad AFR exome AF: 0.564

Gnomad AMR exome AF: 0.707

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.765

Gnomad SAS exome AF: 0.472

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.444

Gnomad OTH exome AF: 0.490

GnomAD4 exome AF: 0.469 AC: 685813 AN: 1460944 Hom.: 165263 Cov.: 42 AF XY: 0.468 AC XY: 339956 AN XY: 726816

Gnomad4 AFR exome AF: 0.568

Gnomad4 AMR exome AF: 0.698

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.774

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.448

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.502 AC: 76160 AN: 151788 Hom.: 19751 Cov.: 31 AF XY: 0.503 AC XY: 37341 AN XY: 74196

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.501

Alfa AF: 0.466 Hom.: 7493

Bravo AF: 0.527

Asia WGS AF: 0.605 AC: 2104 AN: 3478

EpiCase AF: 0.438

EpiControl AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.9
DANN	Benign	0.74

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; COSMIC: COSV57028534;