rs7796553

Variant names:

• chr7-129740403-T-C
• rs7796553
• NM_005011.5:c.1348+13038T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ENSG00000294095 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005011.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	NM_005011.5	MANE Select	c.1348+13038T>C		intron	N/A	NP_005002.3
	NRF1	NM_001293163.2		c.1349-3770T>C		intron	N/A	NP_001280092.1
	NRF1	NM_001040110.2		c.1348+13038T>C		intron	N/A	NP_001035199.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	ENST00000393232.6	TSL:1 MANE Select	c.1348+13038T>C		intron	N/A	ENSP00000376924.1
	NRF1	ENST00000311967.6	TSL:1	c.1349-3770T>C		intron	N/A	ENSP00000309826.2
	NRF1	ENST00000393230.6	TSL:1	c.1348+13038T>C		intron	N/A	ENSP00000376922.2

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

African (AFR) AF: 0.167 AC: 6926 AN: 41538

American (AMR) AF: 0.191 AC: 2917 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 352 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2434 AN: 5160

South Asian (SAS) AF: 0.288 AC: 1387 AN: 4824

European-Finnish (FIN) AF: 0.173 AC: 1832 AN: 10594

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11003 AN: 68006

Other (OTH) AF: 0.167 AC: 352 AN: 2112

Alfa AF: 0.168 Hom.: 6036

Bravo AF: 0.181

Asia WGS AF: 0.364 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.25
PhyloP100		-1.2
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: rs7796553; hg19: chr7-129380243;