rs7101

chr14-75278923-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005252.4(FOS):c.-60C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,601,574 control chromosomes in the GnomAD database, including 430,796 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 (45333 hom., cov: 34)
  • Exomes 𝑓: 0.73 (385463 hom.)
• Consequence: FOS NM_005252.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• 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	UniProt
FOS	NM_005252.4	c.-60C>T		5_prime_UTR_variant	1/4	ENST00000303562.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOS	ENST00000303562.9	c.-60C>T		5_prime_UTR_variant	1/4	1	NM_005252.4	P1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116453 AN: 152088 Hom.: 45304 Cov.: 34

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.742

GnomAD4 exome AF: 0.727 AC: 1053426 AN: 1449368 Hom.: 385463 Cov.: 32 AF XY: 0.723 AC XY: 520791 AN XY: 720668

Gnomad4 AFR exome AF: 0.897

Gnomad4 AMR exome AF: 0.664

Gnomad4 ASJ exome AF: 0.686

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.617

Gnomad4 FIN exome AF: 0.801

Gnomad4 NFE exome AF: 0.738

Gnomad4 OTH exome AF: 0.723

GnomAD4 genome AF: 0.766 AC: 116540 AN: 152206 Hom.: 45333 Cov.: 34 AF XY: 0.761 AC XY: 56656 AN XY: 74414

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.742

Alfa AF: 0.738 Hom.: 52979

Bravo AF: 0.763

Asia WGS AF: 0.592 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	16
Dann	Benign	0.91

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: rs7101; hg19: chr14-75745626; COSMIC: COSV57839174; COSMIC: COSV57839174;