rs10231985

Variant names:

• chr7-129647781-T-A
• rs10231985
• NM_005011.5:c.-6-9565T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-129647781-T-A
• chr7-129647781-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.-6-9565T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,210 control chromosomes in the GnomAD database, including 3,038 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 0.19 (3038 hom., cov: 32)
• Consequence: NRF1 NM_005011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 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.-6-9565T>A		intron	N/A	NP_005002.3
	NRF1	NM_001293163.2		c.-9-9562T>A		intron	N/A	NP_001280092.1
	NRF1	NM_001040110.2		c.-9-9562T>A		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.-6-9565T>A		intron	N/A	ENSP00000376924.1
	NRF1	ENST00000311967.6	TSL:1	c.-9-9562T>A		intron	N/A	ENSP00000309826.2
	NRF1	ENST00000393230.6	TSL:1	c.-9-9562T>A		intron	N/A	ENSP00000376922.2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29024 AN: 152092 Hom.: 3024 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.191 AC: 29061 AN: 152210 Hom.: 3038 Cov.: 32 AF XY: 0.194 AC XY: 14459 AN XY: 74418

African (AFR) AF: 0.182 AC: 7557 AN: 41516

American (AMR) AF: 0.216 AC: 3300 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3472

East Asian (EAS) AF: 0.473 AC: 2447 AN: 5178

South Asian (SAS) AF: 0.296 AC: 1430 AN: 4826

European-Finnish (FIN) AF: 0.185 AC: 1964 AN: 10600

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11463 AN: 68018

Other (OTH) AF: 0.171 AC: 361 AN: 2114

Alfa AF: 0.179 Hom.: 315

Bravo AF: 0.193

Asia WGS AF: 0.372 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.71
PhyloP100		2.1
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: rs10231985; hg19: chr7-129287621;