7-129702203-A-G

Variant names:

• chr7-129702203-A-G
• rs10954252
• NM_005011.5:c.607-6872A>G

Variant summary

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

The NM_005011.5(NRF1):​c.607-6872A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,884 control chromosomes in the GnomAD database, including 17,761 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 0.48 (17761 hom., cov: 31)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRF1	NM_005011.5	c.607-6872A>G		intron_variant	Intron 5 of 10	ENST00000393232.6	NP_005002.3
NRF1	NM_001293163.2	c.607-6872A>G		intron_variant	Intron 5 of 11		NP_001280092.1
NRF1	NM_001040110.2	c.607-6872A>G		intron_variant	Intron 5 of 10		NP_001035199.1
NRF1	NM_001293164.2	c.124-6872A>G		intron_variant	Intron 4 of 9		NP_001280093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6	c.607-6872A>G		intron_variant	Intron 5 of 10	1	NM_005011.5	ENSP00000376924.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72674 AN: 151766 Hom.: 17754 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.479 AC: 72690 AN: 151884 Hom.: 17761 Cov.: 31 AF XY: 0.476 AC XY: 35355 AN XY: 74214

African (AFR) AF: 0.421 AC: 17432 AN: 41398

American (AMR) AF: 0.406 AC: 6190 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2106 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1194 AN: 5168

South Asian (SAS) AF: 0.466 AC: 2240 AN: 4810

European-Finnish (FIN) AF: 0.495 AC: 5222 AN: 10542

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.539 AC: 36637 AN: 67944

Other (OTH) AF: 0.473 AC: 999 AN: 2114

Alfa AF: 0.509 Hom.: 7782

Bravo AF: 0.468

Asia WGS AF: 0.330 AC: 1145 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	16
DANN	Benign	0.71
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs10954252; hg19: chr7-129342043;