14-75280415-G-T

Variant names:

• chr14-75280415-G-T
• rs1063169
• NM_005252.4:c.394-145G>T

Variant summary

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

The NM_005252.4(FOS):​c.394-145G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 709,386 control chromosomes in the GnomAD database, including 8,808 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 0.12 (1449 hom., cov: 33)
  • Exomes 𝑓: 0.16 (7359 hom.)
• Consequence: FOS NM_005252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOS	NM_005252.4	c.394-145G>T		intron_variant	Intron 2 of 3	ENST00000303562.9	NP_005243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOS	ENST00000303562.9	c.394-145G>T		intron_variant	Intron 2 of 3	1	NM_005252.4	ENSP00000306245.4

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18032 AN: 152092 Hom.: 1438 Cov.: 33

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.156 AC: 87108 AN: 557176 Hom.: 7359 Cov.: 7 AF XY: 0.154 AC XY: 44854 AN XY: 291550

Gnomad4 AFR exome AF: 0.0264

Gnomad4 AMR exome AF: 0.0831

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.0984

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.119 AC: 18052 AN: 152210 Hom.: 1449 Cov.: 33 AF XY: 0.117 AC XY: 8734 AN XY: 74398

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.0859

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.0959

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.112

Alfa AF: 0.153 Hom.: 3941

Bravo AF: 0.109

Asia WGS AF: 0.164 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1063169; hg19: chr14-75747118;