rs1962039

Variant names:

• chr7-129711880-G-A
• rs1962039
• NM_005011.5:c.1065+304G>A

Variant summary

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

The NM_005011.5(NRF1):​c.1065+304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,960 control chromosomes in the GnomAD database, including 9,770 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 0.35 (9770 hom., cov: 32)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 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.1065+304G>A		intron	N/A	NP_005002.3
	NRF1	NM_001293163.2		c.1065+304G>A		intron	N/A	NP_001280092.1	Q16656-4
	NRF1	NM_001040110.2		c.1065+304G>A		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.1065+304G>A		intron	N/A	ENSP00000376924.1	Q16656-1
	NRF1	ENST00000311967.6	TSL:1	c.1065+304G>A		intron	N/A	ENSP00000309826.2	Q16656-4
	NRF1	ENST00000393230.6	TSL:1	c.1065+304G>A		intron	N/A	ENSP00000376922.2	Q16656-1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53145 AN: 151842 Hom.: 9748 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.350 AC: 53207 AN: 151960 Hom.: 9770 Cov.: 32 AF XY: 0.354 AC XY: 26293 AN XY: 74252

African (AFR) AF: 0.432 AC: 17883 AN: 41408

American (AMR) AF: 0.343 AC: 5244 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3470

East Asian (EAS) AF: 0.609 AC: 3154 AN: 5176

South Asian (SAS) AF: 0.478 AC: 2303 AN: 4820

European-Finnish (FIN) AF: 0.295 AC: 3111 AN: 10540

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19744 AN: 67956

Other (OTH) AF: 0.332 AC: 701 AN: 2110

Alfa AF: 0.359 Hom.: 4122

Bravo AF: 0.357

Asia WGS AF: 0.528 AC: 1832 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.58
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: rs1962039; hg19: chr7-129351720;