rs7101

Variant names:

• chr14-75278923-C-T
• rs7101
• NM_005252.4:c.-60C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 45 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

FOS-AS1 (HGNC:58290):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005252.4. 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.-60C>T		5_prime_UTR	Exon 1 of 4	NP_005243.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOS	ENST00000303562.9	TSL:1 MANE Select	c.-60C>T		5_prime_UTR	Exon 1 of 4	ENSP00000306245.4
	FOS	ENST00000871987.1		c.-60C>T		5_prime_UTR	Exon 1 of 4	ENSP00000542046.1
	FOS	ENST00000944924.1		c.-60C>T		5_prime_UTR	Exon 1 of 4	ENSP00000614983.1

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

African (AFR) AF: 0.897 AC: 29815 AN: 33244

American (AMR) AF: 0.664 AC: 28850 AN: 43422

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17751 AN: 25874

East Asian (EAS) AF: 0.514 AC: 20137 AN: 39182

South Asian (SAS) AF: 0.617 AC: 52451 AN: 85066

European-Finnish (FIN) AF: 0.801 AC: 40370 AN: 50372

Middle Eastern (MID) AF: 0.740 AC: 4252 AN: 5744

European-Non Finnish (NFE) AF: 0.738 AC: 816557 AN: 1106614

Other (OTH) AF: 0.723 AC: 43243 AN: 59850

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

African (AFR) AF: 0.888 AC: 36893 AN: 41536

American (AMR) AF: 0.665 AC: 10167 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2369 AN: 3470

East Asian (EAS) AF: 0.533 AC: 2756 AN: 5168

South Asian (SAS) AF: 0.601 AC: 2902 AN: 4826

European-Finnish (FIN) AF: 0.794 AC: 8415 AN: 10596

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50511 AN: 67996

Other (OTH) AF: 0.742 AC: 1567 AN: 2112

Alfa AF: 0.741 Hom.: 66637

Bravo AF: 0.763

Asia WGS AF: 0.592 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		0.41
PromoterAI		-0.012	Neutral
Mutation Taster		=299/1	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

Other links and lift over

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