rs10275661

Variant names:

• chr7-129617733-G-A
• rs10275661
• NM_005011.5:c.-7+5909G>A

Variant summary

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

The ENST00000393232.6(NRF1):​c.-7+5909G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,050 control chromosomes in the GnomAD database, including 1,918 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 0.15 (1918 hom., cov: 32)
• Consequence: NRF1 ENST00000393232.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393232.6. 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.-7+5909G>A		intron	N/A	NP_005002.3
	NRF1	NM_001293163.2		c.-10+5909G>A		intron	N/A	NP_001280092.1
	NRF1	NM_001293164.2		c.-378+5909G>A		intron	N/A	NP_001280093.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	ENST00000393232.6	TSL:1 MANE Select	c.-7+5909G>A		intron	N/A	ENSP00000376924.1
	NRF1	ENST00000311967.6	TSL:1	c.-10+5909G>A		intron	N/A	ENSP00000309826.2
	NRF1	ENST00000223190.8	TSL:5	c.-10+5909G>A		intron	N/A	ENSP00000223190.4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23241 AN: 151930 Hom.: 1918 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.153 AC: 23253 AN: 152050 Hom.: 1918 Cov.: 32 AF XY: 0.155 AC XY: 11526 AN XY: 74316

African (AFR) AF: 0.229 AC: 9486 AN: 41448

American (AMR) AF: 0.124 AC: 1889 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3470

East Asian (EAS) AF: 0.137 AC: 709 AN: 5166

South Asian (SAS) AF: 0.165 AC: 794 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1370 AN: 10572

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8116 AN: 67988

Other (OTH) AF: 0.157 AC: 332 AN: 2110

Alfa AF: 0.148 Hom.: 354

Bravo AF: 0.156

Asia WGS AF: 0.154 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.5
DANN	Benign	0.24
PhyloP100		0.36
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: rs10275661; hg19: chr7-129257574;