rs2037244626

Variant names:

• chr17-48051345-A-G
• rs2037244626
• NM_003204.3:c.227A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003204.3(NFE2L1):​c.227A>G​(p.Asn76Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: NFE2L1 NM_003204.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19
• Publications: 0 publications found

Genes affected

NFE2L1 (HGNC:7781): (NFE2 like bZIP transcription factor 1) This gene encodes a protein that is involved in globin gene expression in erythrocytes. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene, NFE2L1, and for "nuclear respiratory factor 1" which has an official symbol of NRF1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17724445).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003204.3. 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
	NFE2L1	NM_003204.3	MANE Select	c.227A>G	p.Asn76Ser	missense	Exon 2 of 6	NP_003195.1	Q14494-1
	NFE2L1	NM_001439152.1		c.227A>G	p.Asn76Ser	missense	Exon 2 of 6	NP_001426081.1
	NFE2L1	NM_001330261.2		c.227A>G	p.Asn76Ser	missense	Exon 2 of 6	NP_001317190.1	J9JIE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFE2L1	ENST00000362042.8	TSL:1 MANE Select	c.227A>G	p.Asn76Ser	missense	Exon 2 of 6	ENSP00000354855.3	Q14494-1
	NFE2L1	ENST00000357480.9	TSL:1	c.227A>G	p.Asn76Ser	missense	Exon 2 of 5	ENSP00000350072.5	Q14494-2
	NFE2L1	ENST00000585291.5	TSL:1	c.227A>G	p.Asn76Ser	missense	Exon 3 of 6	ENSP00000461960.1	Q14494-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152080 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74290

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

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	0.066
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.75	N
PhyloP100		5.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.075
Sift	Benign	0.33	T
Sift4G	Benign	0.46	T
Polyphen		0.0030	B
Vest4		0.11
MutPred		0.26		Gain of disorder (P = 0.0966)
MVP		0.45
MPC		0.34
ClinPred		0.70	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.071
gMVP		0.29

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: rs2037244626; hg19: chr17-46128707;