rs10954252

Positions:

• chr7-129702203-A-G
• chr7-129702203-A-T

Variant summary

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

The NM_005011.5(NRF1):​c.607-6872A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,884 control chromosomes in the GnomAD database, including 17,761 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 0.48 (17761 hom., cov: 31)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRF1	NM_005011.5	c.607-6872A>G		intron_variant		ENST00000393232.6	NP_005002.3
NRF1	NM_001293163.2	c.607-6872A>G		intron_variant			NP_001280092.1
NRF1	NM_001040110.2	c.607-6872A>G		intron_variant			NP_001035199.1
NRF1	NM_001293164.2	c.124-6872A>G		intron_variant			NP_001280093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6	c.607-6872A>G		intron_variant		1	NM_005011.5	ENSP00000376924.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72674 AN: 151766 Hom.: 17754 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.479 AC: 72690 AN: 151884 Hom.: 17761 Cov.: 31 AF XY: 0.476 AC XY: 35355 AN XY: 74214

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.473

Alfa AF: 0.508 Hom.: 6116

Bravo AF: 0.468

Asia WGS AF: 0.330 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs10954252; hg19: chr7-129342043;