chr7-129716366-G-A

Variant names:

• chr7-129716366-G-A
• rs9641855
• NM_005011.5:c.1066-853G>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.1066-853G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,840 control chromosomes in the GnomAD database, including 17,751 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 0.48 (17751 hom., cov: 31)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	NM_005011.5	MANE Select	c.1066-853G>A		intron	N/A	NP_005002.3
	NRF1	NM_001293163.2		c.1066-853G>A		intron	N/A	NP_001280092.1
	NRF1	NM_001040110.2		c.1066-853G>A		intron	N/A	NP_001035199.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	ENST00000393232.6	TSL:1 MANE Select	c.1066-853G>A		intron	N/A	ENSP00000376924.1
	NRF1	ENST00000311967.6	TSL:1	c.1066-853G>A		intron	N/A	ENSP00000309826.2
	NRF1	ENST00000393230.6	TSL:1	c.1066-853G>A		intron	N/A	ENSP00000376922.2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72673 AN: 151720 Hom.: 17725 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.479 AC: 72752 AN: 151840 Hom.: 17751 Cov.: 31 AF XY: 0.485 AC XY: 36020 AN XY: 74224

African (AFR) AF: 0.479 AC: 19842 AN: 41404

American (AMR) AF: 0.574 AC: 8773 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3470

East Asian (EAS) AF: 0.781 AC: 4038 AN: 5172

South Asian (SAS) AF: 0.594 AC: 2856 AN: 4810

European-Finnish (FIN) AF: 0.449 AC: 4718 AN: 10508

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29807 AN: 67894

Other (OTH) AF: 0.461 AC: 971 AN: 2106

Alfa AF: 0.477 Hom.: 9160

Bravo AF: 0.485

Asia WGS AF: 0.652 AC: 2261 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.67
PhyloP100		0.49
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: rs9641855; hg19: chr7-129356206;