rs7796553

chr7-129740403-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005011.5(NRF1):c.1348+13038T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,210 control chromosomes in the GnomAD database, including 2,721 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 0.18 (2721 hom., cov: 32)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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/exons	MANE	UniProt
NRF1	NM_005011.5	c.1348+13038T>C		intron_variant		ENST00000393232.6
NRF1	NM_001040110.2	c.1348+13038T>C		intron_variant
NRF1	NM_001293163.2	c.1349-3770T>C		intron_variant
NRF1	NM_001293164.2	c.865+13038T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRF1	ENST00000393232.6	c.1348+13038T>C		intron_variant		1	NM_005011.5	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27317 AN: 152092 Hom.: 2707 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.180 AC: 27352 AN: 152210 Hom.: 2721 Cov.: 32 AF XY: 0.183 AC XY: 13597 AN XY: 74444

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.167

Alfa AF: 0.166 Hom.: 4498

Bravo AF: 0.181

Asia WGS AF: 0.364 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.21
Dann	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs7796553; hg19: chr7-129380243;