rs6962005

Variant names:

• chr7-129643858-A-G
• rs6962005
• NM_005011.5:c.-6-13488A>G

Variant summary

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

The NM_001293163.2(NRF1):​c.-9-13485A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,164 control chromosomes in the GnomAD database, including 3,588 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 0.19 (3588 hom., cov: 32)
• Consequence: NRF1 NM_001293163.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• 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]

ENSG00000288881 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001293163.2. 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.-6-13488A>G		intron	N/A	NP_005002.3
	NRF1	NM_001293163.2		c.-9-13485A>G		intron	N/A	NP_001280092.1
	NRF1	NM_001040110.2		c.-9-13485A>G		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.-6-13488A>G		intron	N/A	ENSP00000376924.1
	NRF1	ENST00000311967.6	TSL:1	c.-9-13485A>G		intron	N/A	ENSP00000309826.2
	NRF1	ENST00000393230.6	TSL:1	c.-9-13485A>G		intron	N/A	ENSP00000376922.2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29104 AN: 152046 Hom.: 3583 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.191 AC: 29136 AN: 152164 Hom.: 3588 Cov.: 32 AF XY: 0.192 AC XY: 14317 AN XY: 74388

African (AFR) AF: 0.360 AC: 14938 AN: 41472

American (AMR) AF: 0.139 AC: 2125 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3468

East Asian (EAS) AF: 0.136 AC: 701 AN: 5172

South Asian (SAS) AF: 0.171 AC: 827 AN: 4826

European-Finnish (FIN) AF: 0.130 AC: 1376 AN: 10614

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8273 AN: 68008

Other (OTH) AF: 0.182 AC: 384 AN: 2112

Alfa AF: 0.158 Hom.: 804

Bravo AF: 0.198

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		0.45
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: rs6962005; hg19: chr7-129283698;