chr7-129672730-G-A

Variant names:

• chr7-129672730-G-A
• rs10276606
• NM_005011.5:c.338+1187G>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.338+1187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,104 control chromosomes in the GnomAD database, including 2,482 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 0.17 (2482 hom., cov: 31)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRF1	NM_005011.5	c.338+1187G>A		intron_variant	Intron 3 of 10	ENST00000393232.6	NP_005002.3
NRF1	NM_001293163.2	c.338+1187G>A		intron_variant	Intron 3 of 11		NP_001280092.1
NRF1	NM_001040110.2	c.338+1187G>A		intron_variant	Intron 3 of 10		NP_001035199.1
NRF1	NM_001293164.2	c.-145-4902G>A		intron_variant	Intron 2 of 9		NP_001280093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6	c.338+1187G>A		intron_variant	Intron 3 of 10	1	NM_005011.5	ENSP00000376924.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25384 AN: 151986 Hom.: 2469 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.167 AC: 25419 AN: 152104 Hom.: 2482 Cov.: 31 AF XY: 0.171 AC XY: 12745 AN XY: 74344

African (AFR) AF: 0.151 AC: 6257 AN: 41512

American (AMR) AF: 0.212 AC: 3228 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 231 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2439 AN: 5168

South Asian (SAS) AF: 0.279 AC: 1343 AN: 4808

European-Finnish (FIN) AF: 0.152 AC: 1612 AN: 10582

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9825 AN: 67988

Other (OTH) AF: 0.157 AC: 331 AN: 2112

Alfa AF: 0.150 Hom.: 3076

Bravo AF: 0.171

Asia WGS AF: 0.361 AC: 1253 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	0.88
DANN	Benign	0.50
PhyloP100		-0.065
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: rs10276606; hg19: chr7-129312570;