rs6949152

Positions:

• chr7-129646596-A-G
• chr7-129646596-A-T

Variant summary

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

The ENST00000393232.6(NRF1):​c.-6-10750A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,130 control chromosomes in the GnomAD database, including 4,629 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 0.22 (4629 hom., cov: 32)
• Consequence: NRF1 ENST00000393232.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.26

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRF1	NM_005011.5	c.-6-10750A>G		intron_variant		ENST00000393232.6	NP_005002.3
NRF1	NM_001040110.2	c.-9-10747A>G		intron_variant			NP_001035199.1
NRF1	NM_001293163.2	c.-9-10747A>G		intron_variant			NP_001280092.1
NRF1	NM_001293164.2	c.-377-10747A>G		intron_variant			NP_001280093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6	c.-6-10750A>G		intron_variant		1	NM_005011.5	ENSP00000376924	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33987 AN: 152012 Hom.: 4625 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.224 AC: 34019 AN: 152130 Hom.: 4629 Cov.: 32 AF XY: 0.225 AC XY: 16763 AN XY: 74380

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.218

Alfa AF: 0.169 Hom.: 4548

Bravo AF: 0.231

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.048
DANN	Benign	0.62

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: rs6949152; hg19: chr7-129286436;