chr7-129640667-G-A

Variant names:

• chr7-129640667-G-A
• rs10268267
• NM_005011.5:c.-6-16679G>A

Variant summary

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

The NM_005011.5(NRF1):​c.-6-16679G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,040 control chromosomes in the GnomAD database, including 1,214 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 0.13 (1214 hom., cov: 31)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRF1	NM_005011.5	c.-6-16679G>A		intron_variant	Intron 1 of 10	ENST00000393232.6	NP_005002.3
NRF1	NM_001293163.2	c.-9-16676G>A		intron_variant	Intron 1 of 11		NP_001280092.1
NRF1	NM_001040110.2	c.-10+10499G>A		intron_variant	Intron 1 of 10		NP_001035199.1
NRF1	NM_001293164.2	c.-377-16676G>A		intron_variant	Intron 1 of 9		NP_001280093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6	c.-6-16679G>A		intron_variant	Intron 1 of 10	1	NM_005011.5	ENSP00000376924.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19150 AN: 151922 Hom.: 1213 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.126 AC: 19163 AN: 152040 Hom.: 1214 Cov.: 31 AF XY: 0.128 AC XY: 9538 AN XY: 74296

African (AFR) AF: 0.137 AC: 5663 AN: 41460

American (AMR) AF: 0.113 AC: 1723 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3470

East Asian (EAS) AF: 0.134 AC: 693 AN: 5164

South Asian (SAS) AF: 0.170 AC: 818 AN: 4816

European-Finnish (FIN) AF: 0.130 AC: 1370 AN: 10566

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8126 AN: 67960

Other (OTH) AF: 0.129 AC: 272 AN: 2112

Alfa AF: 0.120 Hom.: 261

Bravo AF: 0.125

Asia WGS AF: 0.150 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.67
DANN	Benign	0.59
PhyloP100		-0.39
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: rs10268267; hg19: chr7-129280508;