rs10231985

chr7-129647781-T-Achr7-129647781-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.-6-9565T>A 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 152,210 control chromosomes in the GnomAD database, including 3,038 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 (3038 hom., cov: 32)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRF1	NM_005011.5	c.-6-9565T>A		intron_variant		ENST00000393232.6
NRF1	NM_001040110.2	c.-9-9562T>A		intron_variant
NRF1	NM_001293163.2	c.-9-9562T>A		intron_variant
NRF1	NM_001293164.2	c.-377-9562T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRF1	ENST00000393232.6	c.-6-9565T>A		intron_variant		1	NM_005011.5	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29024 AN: 152092 Hom.: 3024 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.191 AC: 29061 AN: 152210 Hom.: 3038 Cov.: 32 AF XY: 0.194 AC XY: 14459 AN XY: 74418

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.171

Alfa AF: 0.179 Hom.: 315

Bravo AF: 0.193

Asia WGS AF: 0.372 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.3
Dann	Benign	0.71

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: rs10231985; hg19: chr7-129287621;