7-26152630-C-A

Variant names:

• chr7-26152630-C-A
• rs1204227710
• NM_004289.7:c.132C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004289.7(NFE2L3):​c.132C>A​(p.Asp44Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,378,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: NFE2L3 NM_004289.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.524
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053935558).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004289.7. 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
	NFE2L3	NM_004289.7	MANE Select	c.132C>A	p.Asp44Glu	missense	Exon 1 of 4	NP_004280.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L3	ENST00000056233.4	TSL:1 MANE Select	c.132C>A	p.Asp44Glu	missense	Exon 1 of 4	ENSP00000056233.3	Q9Y4A8
	NFE2L3	ENST00000927668.1		c.132C>A	p.Asp44Glu	missense	Exon 1 of 4	ENSP00000597727.1
	NFE2L3	ENST00000927666.1		c.132C>A	p.Asp44Glu	missense	Exon 1 of 4	ENSP00000597725.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1378260 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683248

African (AFR) AF: 0.00 AC: 0 AN: 28910

American (AMR) AF: 0.00 AC: 0 AN: 35214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24332

East Asian (EAS) AF: 0.00 AC: 0 AN: 32458

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5530

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081354

Other (OTH) AF: 0.00 AC: 0 AN: 57432

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.73
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.52
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.022
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0060	B
Vest4		0.12
MutPred		0.33		Gain of catalytic residue at D44 (P = 0.0186)
MVP		0.18
MPC		1.8
ClinPred		0.078	T
GERP RS		-1.1
PromoterAI		0.063	Neutral
Varity_R		0.019
gMVP		0.26
Mutation Taster		=96/4	polymorphism

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: rs1204227710; hg19: chr7-26192250; COSMIC: COSV50226655;