14-75283172-G-A

Variant names:

• chr14-75283172-G-A
• rs4645869
• ENST00000535987.6:c.*1748G>A

Variant summary

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

The ENST00000535987.6(FOS):​c.*1748G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 152,284 control chromosomes in the GnomAD database, including 187 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 0.036 (187 hom., cov: 33)
• Consequence: FOS ENST00000535987.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 5 publications found

Genes affected

FOS (HGNC:3796): (Fos proto-oncogene, 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. In some cases, expression of the FOS gene has also been associated with apoptotic cell death. [provided by RefSeq, Jul 2008]

FOS Gene-Disease associations (from GenCC):

• Berardinelli-Seip congenital lipodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000535987.6. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOS	ENST00000535987.6	TSL:2	c.*1748G>A		3_prime_UTR	Exon 3 of 3	ENSP00000442268.1

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5462 AN: 152166 Hom.: 181 Cov.: 33

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.00895

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0301

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

GnomAD4 genome AF: 0.0361 AC: 5497 AN: 152284 Hom.: 187 Cov.: 33 AF XY: 0.0375 AC XY: 2795 AN XY: 74472

African (AFR) AF: 0.0513 AC: 2132 AN: 41570

American (AMR) AF: 0.0381 AC: 583 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00895 AC: 31 AN: 3464

East Asian (EAS) AF: 0.182 AC: 943 AN: 5186

South Asian (SAS) AF: 0.0429 AC: 207 AN: 4826

European-Finnish (FIN) AF: 0.0320 AC: 339 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0167 AC: 1134 AN: 68024

Other (OTH) AF: 0.0317 AC: 67 AN: 2114

Alfa AF: 0.0282 Hom.: 189

Bravo AF: 0.0379

Asia WGS AF: 0.0950 AC: 330 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	1.4
DANN	Benign	0.56
PhyloP100		-0.080

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4645869; hg19: chr14-75749875;