rs1180670857

Variant names:

• chr7-26152899-C-A
• rs1180670857
• NM_004289.7:c.401C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-26152899-C-A
• chr7-26152899-C-G
• chr7-26152899-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004289.7(NFE2L3):​c.401C>A​(p.Ser134*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000386 in 1,296,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: NFE2L3 NM_004289.7 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298
• Publications: 0 publications found

Genes affected

NFE2L3 (HGNC:7783): (NFE2 like bZIP transcription factor 3) This gene encodes a member of the cap 'n' collar basic-region leucine zipper family of transcription factors. The encoded protein heterodimerizes with small musculoaponeurotic fibrosarcoma factors to bind antioxidant response elements in target genes. This protein is a membrane bound glycoprotein that is targeted to the endoplasmic reticulum and the nuclear envelope. Pseudogenes of this gene are found on chromosomes 16, 17, and 18. [provided by RefSeq, Mar 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L3	NM_004289.7	c.401C>A	p.Ser134*	stop_gained	Exon 1 of 4	ENST00000056233.4	NP_004280.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L3	ENST00000056233.4	c.401C>A	p.Ser134*	stop_gained	Exon 1 of 4	1	NM_004289.7	ENSP00000056233.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 52850 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000386 AC: 5 AN: 1296970 Hom.: 0 Cov.: 31 AF XY: 0.00000313 AC XY: 2 AN XY: 638458

African (AFR) AF: 0.00 AC: 0 AN: 25740

American (AMR) AF: 0.00 AC: 0 AN: 19954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21722

East Asian (EAS) AF: 0.00 AC: 0 AN: 28306

South Asian (SAS) AF: 0.00 AC: 0 AN: 67678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3824

European-Non Finnish (NFE) AF: 0.00000479 AC: 5 AN: 1043708

Other (OTH) AF: 0.00 AC: 0 AN: 53754

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.47	N
PhyloP100		0.30
Vest4		0.12
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=27/173	disease causing (fs/PTC)

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: rs1180670857; hg19: chr7-26192519;