rs7781972

Variant names:

• chr7-129619951-T-A
• rs7781972
• NM_005011.5:c.-7+8127T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-129619951-T-A
• chr7-129619951-T-C
• chr7-129619951-T-G

Variant summary

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

The NM_005011.5(NRF1):​c.-7+8127T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,758 control chromosomes in the GnomAD database, including 17,107 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 0.45 (17107 hom., cov: 30)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRF1	NM_005011.5	c.-7+8127T>A		intron_variant	Intron 1 of 10	ENST00000393232.6	NP_005002.3
NRF1	NM_001293163.2	c.-10+8127T>A		intron_variant	Intron 1 of 11		NP_001280092.1
NRF1	NM_001293164.2	c.-378+8127T>A		intron_variant	Intron 1 of 9		NP_001280093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6	c.-7+8127T>A		intron_variant	Intron 1 of 10	1	NM_005011.5	ENSP00000376924.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67623 AN: 151636 Hom.: 17074 Cov.: 30

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.446 AC: 67709 AN: 151758 Hom.: 17107 Cov.: 30 AF XY: 0.451 AC XY: 33414 AN XY: 74170

African (AFR) AF: 0.683 AC: 28240 AN: 41326

American (AMR) AF: 0.398 AC: 6078 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3470

East Asian (EAS) AF: 0.668 AC: 3431 AN: 5140

South Asian (SAS) AF: 0.494 AC: 2382 AN: 4818

European-Finnish (FIN) AF: 0.345 AC: 3622 AN: 10508

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21901 AN: 67920

Other (OTH) AF: 0.413 AC: 871 AN: 2110

Alfa AF: 0.388 Hom.: 1575

Bravo AF: 0.460

Asia WGS AF: 0.577 AC: 2008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.78
PhyloP100		-0.41
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: rs7781972; hg19: chr7-129259792;