rs2239615

Variant names:

• chr14-75278848-T-A
• rs2239615
• NM_005252.4:c.-135T>A

Your query was ambiguous. Multiple possible variants found:

• chr14-75278848-T-A
• chr14-75278848-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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

ENSG00000258740 (HGNC:58290):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000303562.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOS	NM_005252.4	MANE Select	c.-135T>A		5_prime_UTR	Exon 1 of 4	NP_005243.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOS	ENST00000303562.9	TSL:1 MANE Select	c.-135T>A		5_prime_UTR	Exon 1 of 4	ENSP00000306245.4
	FOS	ENST00000556324.2	TSL:3	n.21T>A		non_coding_transcript_exon	Exon 1 of 2
	FOS	ENST00000535987.6	TSL:2	c.-135T>A		5_prime_UTR	Exon 1 of 3	ENSP00000442268.1

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

African (AFR) AF: 0.897 AC: 18232 AN: 20318

American (AMR) AF: 0.677 AC: 16127 AN: 23838

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 12364 AN: 17892

East Asian (EAS) AF: 0.509 AC: 16665 AN: 32734

South Asian (SAS) AF: 0.621 AC: 37357 AN: 60132

European-Finnish (FIN) AF: 0.801 AC: 28312 AN: 35344

Middle Eastern (MID) AF: 0.736 AC: 3243 AN: 4406

European-Non Finnish (NFE) AF: 0.744 AC: 466426 AN: 626636

Other (OTH) AF: 0.726 AC: 29115 AN: 40110

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

African (AFR) AF: 0.889 AC: 36946 AN: 41562

American (AMR) AF: 0.665 AC: 10171 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3472

East Asian (EAS) AF: 0.533 AC: 2754 AN: 5164

South Asian (SAS) AF: 0.602 AC: 2903 AN: 4826

European-Finnish (FIN) AF: 0.795 AC: 8423 AN: 10594

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

European-Non Finnish (NFE) AF: 0.743 AC: 50515 AN: 67986

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		0.42
PromoterAI		0.10	Neutral
Mutation Taster		=296/4	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: rs2239615; hg19: chr14-75745551;