11-65893177-C-T

Variant names:

• chr11-65893177-C-T
• rs114787843
• NM_005438.5:c.525G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005438.5(FOSL1):​c.525G>A​(p.Pro175Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,613,826 control chromosomes in the GnomAD database, including 324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (167 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (157 hom.)
• Consequence: FOSL1 NM_005438.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.14
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-65893177-C-T is Benign according to our data. Variant chr11-65893177-C-T is described in ClinVar as Benign. ClinVar VariationId is 787377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0863 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL1	NM_005438.5	MANE Select	c.525G>A	p.Pro175Pro	synonymous	Exon 4 of 4	NP_005429.1	A0A0S2Z595
	FOSL1	NM_001300844.2		c.417G>A	p.Pro139Pro	synonymous	Exon 3 of 3	NP_001287773.1	E9PPX2
	FOSL1	NM_001300856.2		c.327G>A	p.Pro109Pro	synonymous	Exon 3 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.525G>A	p.Pro175Pro	synonymous	Exon 4 of 4	ENSP00000310170.2	P15407-1
	FOSL1	ENST00000531493.5	TSL:1	c.417G>A	p.Pro139Pro	synonymous	Exon 3 of 3	ENSP00000436276.1	E9PPX2
	FOSL1	ENST00000913992.1		c.522G>A	p.Pro174Pro	synonymous	Exon 4 of 4	ENSP00000584051.1

Frequencies

GnomAD3 genomes AF: 0.0255 AC: 3877 AN: 152074 Hom.: 166 Cov.: 32

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00923

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00683 AC: 1715 AN: 251048 AF XY: 0.00471

Gnomad AFR exome AF: 0.0918

Gnomad AMR exome AF: 0.00402

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000509

Gnomad NFE exome AF: 0.000458

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00284 AC: 4157 AN: 1461634 Hom.: 157 Cov.: 32 AF XY: 0.00243 AC XY: 1767 AN XY: 727108

African (AFR) AF: 0.0931 AC: 3115 AN: 33474

American (AMR) AF: 0.00470 AC: 210 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86232

European-Finnish (FIN) AF: 0.000393 AC: 21 AN: 53404

Middle Eastern (MID) AF: 0.00321 AC: 18 AN: 5610

European-Non Finnish (NFE) AF: 0.000329 AC: 366 AN: 1111986

Other (OTH) AF: 0.00663 AC: 400 AN: 60374

GnomAD4 genome AF: 0.0256 AC: 3891 AN: 152192 Hom.: 167 Cov.: 32 AF XY: 0.0238 AC XY: 1773 AN XY: 74422

African (AFR) AF: 0.0887 AC: 3679 AN: 41470

American (AMR) AF: 0.00922 AC: 141 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000471 AC: 32 AN: 68004

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.0211 Hom.: 94

Bravo AF: 0.0287

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.14
DANN	Benign	0.80
PhyloP100		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs114787843; hg19: chr11-65660648; COSMIC: COSV57028669; COSMIC: COSV57028669;