rs7781972

chr7-129619951-T-Achr7-129619951-T-Cchr7-129619951-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005011.5(NRF1):c.-7+8127T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,758 control chromosomes in the GnomAD database, including 17,107 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 0.45 (17107 hom., cov: 30)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

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

Verdict is Benign. Variant got -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 = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRF1	NM_005011.5	c.-7+8127T>A		intron_variant		ENST00000393232.6
NRF1	NM_001293163.2	c.-10+8127T>A		intron_variant
NRF1	NM_001293164.2	c.-378+8127T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRF1	ENST00000393232.6	c.-7+8127T>A		intron_variant		1	NM_005011.5	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67623 AN: 151636 Hom.: 17074 Cov.: 30

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.446 AC: 67709 AN: 151758 Hom.: 17107 Cov.: 30 AF XY: 0.451 AC XY: 33414 AN XY: 74170

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.413

Alfa AF: 0.388 Hom.: 1575

Bravo AF: 0.460

Asia WGS AF: 0.577 AC: 2008 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	2.4
Dann	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs7781972; hg19: chr7-129259792;