7-129619902-C-T

Variant names:

• chr7-129619902-C-T
• rs10225103
• NM_005011.5:c.-7+8078C>T

Variant summary

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

The NM_005011.5(NRF1):​c.-7+8078C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,528 control chromosomes in the GnomAD database, including 5,551 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 0.22 (5551 hom., cov: 29)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 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.-7+8078C>T		intron	N/A	NP_005002.3
	NRF1	NM_001293163.2		c.-10+8078C>T		intron	N/A	NP_001280092.1	Q16656-4
	NRF1	NM_001293164.2		c.-378+8078C>T		intron	N/A	NP_001280093.1	Q16656-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	ENST00000393232.6	TSL:1 MANE Select	c.-7+8078C>T		intron	N/A	ENSP00000376924.1	Q16656-1
	NRF1	ENST00000311967.6	TSL:1	c.-10+8078C>T		intron	N/A	ENSP00000309826.2	Q16656-4
	NRF1	ENST00000928009.1		c.-7+8078C>T		intron	N/A	ENSP00000598068.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33731 AN: 151408 Hom.: 5541 Cov.: 29

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.183

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.223 AC: 33773 AN: 151528 Hom.: 5551 Cov.: 29 AF XY: 0.223 AC XY: 16492 AN XY: 74032

African (AFR) AF: 0.470 AC: 19391 AN: 41214

American (AMR) AF: 0.150 AC: 2280 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3468

East Asian (EAS) AF: 0.137 AC: 706 AN: 5140

South Asian (SAS) AF: 0.166 AC: 799 AN: 4814

European-Finnish (FIN) AF: 0.130 AC: 1361 AN: 10454

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.121 AC: 8242 AN: 67910

Other (OTH) AF: 0.205 AC: 428 AN: 2090

Alfa AF: 0.144 Hom.: 2738

Bravo AF: 0.235

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.65
PhyloP100		-0.31
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: rs10225103; hg19: chr7-129259743;