chr11-65896875-T-C

Variant names:

• chr11-65896875-T-C
• rs637571
• NM_005438.5:c.231A>G
• FOSL1 p.Gln77Gln

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 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 -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.

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.231A>G	p.Gln77Gln	synonymous	Exon 2 of 4	NP_005429.1	A0A0S2Z595
	FOSL1	NM_001300844.2		c.231A>G	p.Gln77Gln	synonymous	Exon 2 of 3	NP_001287773.1	E9PPX2
	FOSL1	NM_001300855.2		c.231A>G	p.Gln77Gln	synonymous	Exon 2 of 4	NP_001287784.1	E9PKL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL1	ENST00000312562.7	TSL:1 MANE Select	c.231A>G	p.Gln77Gln	synonymous	Exon 2 of 4	ENSP00000310170.2	P15407-1
	FOSL1	ENST00000531493.5	TSL:1	c.231A>G	p.Gln77Gln	synonymous	Exon 2 of 3	ENSP00000436276.1	E9PPX2
	FOSL1	ENST00000913992.1		c.228A>G	p.Gln76Gln	synonymous	Exon 2 of 4	ENSP00000584051.1

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

GnomAD2 exomes AF: 0.514 AC: 128891 AN: 250844 AF XY: 0.501

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 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

African (AFR) AF: 0.568 AC: 19027 AN: 33470

American (AMR) AF: 0.698 AC: 31196 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 12842 AN: 26122

East Asian (EAS) AF: 0.774 AC: 30725 AN: 39698

South Asian (SAS) AF: 0.476 AC: 41012 AN: 86226

European-Finnish (FIN) AF: 0.400 AC: 21346 AN: 53400

Middle Eastern (MID) AF: 0.423 AC: 2437 AN: 5758

European-Non Finnish (NFE) AF: 0.448 AC: 498047 AN: 1111204

Other (OTH) AF: 0.483 AC: 29181 AN: 60360

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

African (AFR) AF: 0.566 AC: 23407 AN: 41362

American (AMR) AF: 0.607 AC: 9257 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3468

East Asian (EAS) AF: 0.761 AC: 3924 AN: 5154

South Asian (SAS) AF: 0.490 AC: 2355 AN: 4810

European-Finnish (FIN) AF: 0.381 AC: 4011 AN: 10520

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29906 AN: 67912

Other (OTH) AF: 0.501 AC: 1054 AN: 2102

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.9
DANN	Benign	0.74
PhyloP100		-0.085
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs637571;

hg19: chr11-65664346;

COSMIC: COSV57028534;