14-75278744-C-T

Variant names:

• chr14-75278744-C-T
• rs4645852
• ENST00000789958.1:n.447+336G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000789958.1(FOS-AS1):​n.447+336G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 361,636 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: FOS-AS1 ENST00000789958.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 0 publications found

Genes affected

FOS-AS1 (HGNC:58290):

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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000789958.1. 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
	FOS	NM_005252.4	MANE Select	c.-239C>T		upstream_gene	N/A	NP_005243.1	P01100-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOS-AS1	ENST00000789958.1		n.447+336G>A		intron	N/A
	FOS	ENST00000303562.9	TSL:1 MANE Select	c.-239C>T		upstream_gene	N/A	ENSP00000306245.4	P01100-1
	FOS	ENST00000871987.1		c.-239C>T		upstream_gene	N/A	ENSP00000542046.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000277 AC: 1 AN: 361636 Hom.: 0 Cov.: 4 AF XY: 0.00000524 AC XY: 1 AN XY: 190726

African (AFR) AF: 0.00 AC: 0 AN: 7340

American (AMR) AF: 0.00 AC: 0 AN: 10306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10716

East Asian (EAS) AF: 0.00 AC: 0 AN: 20324

South Asian (SAS) AF: 0.00 AC: 0 AN: 39754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1596

European-Non Finnish (NFE) AF: 0.00000443 AC: 1 AN: 225770

Other (OTH) AF: 0.00 AC: 0 AN: 21036

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	0.72
DANN	Benign	0.84
PhyloP100		-2.5
PromoterAI		-0.38	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4645852; hg19: chr14-75745447;