7-129657492-T-G

Variant names:

• chr7-129657492-T-G
• rs1882094
• NM_005011.5:c.141T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005011.5(NRF1):​c.141T>G​(p.Ser47Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,613,256 control chromosomes in the GnomAD database, including 101,771 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 0.42 (15725 hom., cov: 31)
  • Exomes 𝑓: 0.33 (86046 hom.)
• Consequence: NRF1 NM_005011.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 31 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-1.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRF1	NM_005011.5	c.141T>G	p.Ser47Ser	synonymous_variant	Exon 2 of 11	ENST00000393232.6	NP_005002.3
NRF1	NM_001293163.2	c.141T>G	p.Ser47Ser	synonymous_variant	Exon 2 of 12		NP_001280092.1
NRF1	NM_001040110.2	c.141T>G	p.Ser47Ser	synonymous_variant	Exon 2 of 11		NP_001035199.1
NRF1	NM_001293164.2	c.-228T>G		5_prime_UTR_variant	Exon 2 of 10		NP_001280093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6	c.141T>G	p.Ser47Ser	synonymous_variant	Exon 2 of 11	1	NM_005011.5	ENSP00000376924.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63850 AN: 151700 Hom.: 15694 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.370

GnomAD2 exomes AF: 0.381 AC: 95731 AN: 251434 AF XY: 0.376

Gnomad AFR exome AF: 0.686

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.634

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.331 AC: 483127 AN: 1461440 Hom.: 86046 Cov.: 38 AF XY: 0.333 AC XY: 242021 AN XY: 727064

African (AFR) AF: 0.692 AC: 23166 AN: 33472

American (AMR) AF: 0.395 AC: 17663 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5828 AN: 26132

East Asian (EAS) AF: 0.615 AC: 24409 AN: 39700

South Asian (SAS) AF: 0.475 AC: 40963 AN: 86244

European-Finnish (FIN) AF: 0.312 AC: 16686 AN: 53412

Middle Eastern (MID) AF: 0.295 AC: 1701 AN: 5766

European-Non Finnish (NFE) AF: 0.298 AC: 331658 AN: 1111608

Other (OTH) AF: 0.349 AC: 21053 AN: 60384

GnomAD4 genome AF: 0.421 AC: 63928 AN: 151816 Hom.: 15725 Cov.: 31 AF XY: 0.424 AC XY: 31441 AN XY: 74204

African (AFR) AF: 0.677 AC: 28043 AN: 41400

American (AMR) AF: 0.368 AC: 5600 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 758 AN: 3466

East Asian (EAS) AF: 0.608 AC: 3141 AN: 5162

South Asian (SAS) AF: 0.468 AC: 2255 AN: 4814

European-Finnish (FIN) AF: 0.315 AC: 3307 AN: 10486

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19741 AN: 67952

Other (OTH) AF: 0.374 AC: 788 AN: 2108

Alfa AF: 0.332 Hom.: 30757

Bravo AF: 0.435

Asia WGS AF: 0.542 AC: 1885 AN: 3478

EpiCase AF: 0.289

EpiControl AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.2
DANN	Benign	0.63
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=291/9	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: rs1882094; hg19: chr7-129297332; COSMIC: COSV56212312;