14-75278848-T-A

Position:

• chr14-75278848-T-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000303562.9(FOS):​c.-135T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 1,013,622 control chromosomes in the GnomAD database, including 276,112 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 0.77 (45376 hom., cov: 34)
  • Exomes 𝑓: 0.73 (230736 hom.)
• Consequence: FOS ENST00000303562.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOS	NM_005252.4	c.-135T>A		5_prime_UTR_variant	1/4	ENST00000303562.9	NP_005243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOS	ENST00000303562.9	c.-135T>A		5_prime_UTR_variant	1/4	1	NM_005252.4	ENSP00000306245	P1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116513 AN: 152094 Hom.: 45341 Cov.: 34

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.742

GnomAD4 exome AF: 0.729 AC: 627841 AN: 861410 Hom.: 230736 Cov.: 11 AF XY: 0.724 AC XY: 316774 AN XY: 437830

Gnomad4 AFR exome AF: 0.897

Gnomad4 AMR exome AF: 0.677

Gnomad4 ASJ exome AF: 0.691

Gnomad4 EAS exome AF: 0.509

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.801

Gnomad4 NFE exome AF: 0.744

Gnomad4 OTH exome AF: 0.726

GnomAD4 genome AF: 0.766 AC: 116609 AN: 152212 Hom.: 45376 Cov.: 34 AF XY: 0.762 AC XY: 56685 AN XY: 74404

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.742

Alfa AF: 0.774 Hom.: 5730

Bravo AF: 0.764

Asia WGS AF: 0.595 AC: 2069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	16
DANN	Benign	0.92

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: rs2239615; hg19: chr14-75745551;