7-129753501-A-G

Variant names:

• chr7-129753501-A-G
• rs10500120
• NM_005011.5:c.1349-1517A>G

Variant summary

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

The NM_005011.5(NRF1):​c.1349-1517A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,134 control chromosomes in the GnomAD database, including 7,287 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 0.31 (7287 hom., cov: 33)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRF1	NM_005011.5	c.1349-1517A>G		intron_variant	Intron 10 of 10	ENST00000393232.6	NP_005002.3
NRF1	NM_001293163.2	c.1406-1517A>G		intron_variant	Intron 11 of 11		NP_001280092.1
NRF1	NM_001040110.2	c.1349-1517A>G		intron_variant	Intron 10 of 10		NP_001035199.1
NRF1	NM_001293164.2	c.866-1517A>G		intron_variant	Intron 9 of 9		NP_001280093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6	c.1349-1517A>G		intron_variant	Intron 10 of 10	1	NM_005011.5	ENSP00000376924.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46776 AN: 152016 Hom.: 7282 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.308 AC: 46818 AN: 152134 Hom.: 7287 Cov.: 33 AF XY: 0.310 AC XY: 23058 AN XY: 74370

African (AFR) AF: 0.310 AC: 12854 AN: 41480

American (AMR) AF: 0.384 AC: 5866 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1039 AN: 3468

East Asian (EAS) AF: 0.320 AC: 1652 AN: 5170

South Asian (SAS) AF: 0.308 AC: 1483 AN: 4822

European-Finnish (FIN) AF: 0.286 AC: 3025 AN: 10580

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19948 AN: 68010

Other (OTH) AF: 0.305 AC: 644 AN: 2112

Alfa AF: 0.302 Hom.: 8891

Bravo AF: 0.312

Asia WGS AF: 0.296 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
DANN	Benign	0.61
PhyloP100		-0.16
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: rs10500120; hg19: chr7-129393341;