rs6948697

Variant names:

• chr7-129741316-C-G
• rs6948697
• NM_005011.5:c.1349-13702C>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.1349-13702C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,988 control chromosomes in the GnomAD database, including 19,230 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 0.49 (19230 hom., cov: 31)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 7 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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 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.1349-13702C>G		intron	N/A	NP_005002.3
	NRF1	NM_001293163.2		c.1349-2857C>G		intron	N/A	NP_001280092.1	Q16656-4
	NRF1	NM_001040110.2		c.1349-13702C>G		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.1349-13702C>G		intron	N/A	ENSP00000376924.1	Q16656-1
	NRF1	ENST00000311967.6	TSL:1	c.1349-2857C>G		intron	N/A	ENSP00000309826.2	Q16656-4
	NRF1	ENST00000393230.6	TSL:1	c.1349-13702C>G		intron	N/A	ENSP00000376922.2	Q16656-1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74388 AN: 151870 Hom.: 19224 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.490 AC: 74429 AN: 151988 Hom.: 19230 Cov.: 31 AF XY: 0.489 AC XY: 36353 AN XY: 74294

African (AFR) AF: 0.316 AC: 13074 AN: 41414

American (AMR) AF: 0.450 AC: 6879 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2058 AN: 3468

East Asian (EAS) AF: 0.564 AC: 2914 AN: 5168

South Asian (SAS) AF: 0.564 AC: 2714 AN: 4808

European-Finnish (FIN) AF: 0.548 AC: 5794 AN: 10578

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39290 AN: 67960

Other (OTH) AF: 0.482 AC: 1018 AN: 2112

Alfa AF: 0.565 Hom.: 13600

Bravo AF: 0.477

Asia WGS AF: 0.531 AC: 1846 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	5.3
DANN	Benign	0.64
PhyloP100		-0.13
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: rs6948697; hg19: chr7-129381156;