7-129632518-G-A

Variant names:

• chr7-129632518-G-A
• rs6969098
• NM_005011.5:c.-7+20694G>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.-7+20694G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,722 control chromosomes in the GnomAD database, including 3,114 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 (3114 hom., cov: 31)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRF1	NM_005011.5	c.-7+20694G>A		intron_variant	Intron 1 of 10	ENST00000393232.6	NP_005002.3
NRF1	NM_001293163.2	c.-10+20694G>A		intron_variant	Intron 1 of 11		NP_001280092.1
NRF1	NM_001040110.2	c.-10+2350G>A		intron_variant	Intron 1 of 10		NP_001035199.1
NRF1	NM_001293164.2	c.-378+20694G>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.-7+20694G>A		intron_variant	Intron 1 of 10	1	NM_005011.5	ENSP00000376924.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29289 AN: 151602 Hom.: 3099 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.193 AC: 29330 AN: 151722 Hom.: 3114 Cov.: 31 AF XY: 0.197 AC XY: 14600 AN XY: 74142

African (AFR) AF: 0.196 AC: 8104 AN: 41340

American (AMR) AF: 0.218 AC: 3323 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2437 AN: 5150

South Asian (SAS) AF: 0.298 AC: 1431 AN: 4802

European-Finnish (FIN) AF: 0.185 AC: 1947 AN: 10506

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

European-Non Finnish (NFE) AF: 0.165 AC: 11193 AN: 67900

Other (OTH) AF: 0.169 AC: 355 AN: 2106

Alfa AF: 0.180 Hom.: 333

Bravo AF: 0.195

Asia WGS AF: 0.375 AC: 1303 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-0.0040
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: rs6969098; hg19: chr7-129272359;