rs2402970

Variant names:

• chr7-129739961-C-T
• rs2402970
• NM_005011.5:c.1348+12596C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005011.5(NRF1):​c.1348+12596C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,118 control chromosomes in the GnomAD database, including 2,418 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 0.17 (2418 hom., cov: 32)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410
• Publications: 6 publications found

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]

ENSG00000294095 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005011.5. 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
	NRF1	NM_005011.5	MANE Select	c.1348+12596C>T		intron	N/A	NP_005002.3
	NRF1	NM_001293163.2		c.1349-4212C>T		intron	N/A	NP_001280092.1	Q16656-4
	NRF1	NM_001040110.2		c.1348+12596C>T		intron	N/A	NP_001035199.1	Q16656-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	ENST00000393232.6	TSL:1 MANE Select	c.1348+12596C>T		intron	N/A	ENSP00000376924.1	Q16656-1
	NRF1	ENST00000311967.6	TSL:1	c.1349-4212C>T		intron	N/A	ENSP00000309826.2	Q16656-4
	NRF1	ENST00000393230.6	TSL:1	c.1348+12596C>T		intron	N/A	ENSP00000376922.2	Q16656-1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25502 AN: 152000 Hom.: 2416 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0914

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.168 AC: 25531 AN: 152118 Hom.: 2418 Cov.: 32 AF XY: 0.169 AC XY: 12579 AN XY: 74358

African (AFR) AF: 0.268 AC: 11134 AN: 41468

American (AMR) AF: 0.149 AC: 2280 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3472

East Asian (EAS) AF: 0.137 AC: 710 AN: 5170

South Asian (SAS) AF: 0.189 AC: 913 AN: 4822

European-Finnish (FIN) AF: 0.120 AC: 1275 AN: 10594

Middle Eastern (MID) AF: 0.166 AC: 48 AN: 290

European-Non Finnish (NFE) AF: 0.123 AC: 8349 AN: 67996

Other (OTH) AF: 0.162 AC: 341 AN: 2110

Alfa AF: 0.139 Hom.: 975

Bravo AF: 0.173

Asia WGS AF: 0.166 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.55
PhyloP100		0.41
Mutation Taster		=100/0	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: rs2402970; hg19: chr7-129379801; COSMIC: COSV56212344;