rs2402976

Positions:

• chr7-129702564-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005011.5(NRF1):​c.607-6511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,950 control chromosomes in the GnomAD database, including 16,282 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 0.45 (16282 hom., cov: 32)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

Genes affected

NRF1 (HGNC:7996): (nuclear respiratory factor 1) This gene encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternative splicing results in multiple transcript variants. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor (erythroid-derived 2)-like 1" which has an official symbol of NFE2L1. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRF1	NM_005011.5	c.607-6511G>A		intron_variant		ENST00000393232.6	NP_005002.3
NRF1	NM_001040110.2	c.607-6511G>A		intron_variant			NP_001035199.1
NRF1	NM_001293163.2	c.607-6511G>A		intron_variant			NP_001280092.1
NRF1	NM_001293164.2	c.124-6511G>A		intron_variant			NP_001280093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6	c.607-6511G>A		intron_variant		1	NM_005011.5	ENSP00000376924	P1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68759 AN: 151830 Hom.: 16281 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.452 AC: 68757 AN: 151950 Hom.: 16282 Cov.: 32 AF XY: 0.451 AC XY: 33504 AN XY: 74272

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.456

Alfa AF: 0.527 Hom.: 33172

Bravo AF: 0.439

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.9
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2402976; hg19: chr7-129342404;