NM_005011.5:c.1233C>T

Variant names:

• chr7-129727250-C-T
• rs149764867
• NM_005011.5:c.1233C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_005011.5(NRF1):​c.1233C>T​(p.Ala411Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,594,170 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (11 hom.)
• Consequence: NRF1 NM_005011.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0800
• Publications: 0 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]

ENSG00000294095 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 7-129727250-C-T is Benign according to our data. Variant chr7-129727250-C-T is described in ClinVar as Benign. ClinVar VariationId is 782028.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.08 with no splicing effect.
• BS2: High AC in GnomAd4 at 263 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	NM_005011.5	MANE Select	c.1233C>T	p.Ala411Ala	synonymous	Exon 10 of 11	NP_005002.3
	NRF1	NM_001293163.2		c.1233C>T	p.Ala411Ala	synonymous	Exon 10 of 12	NP_001280092.1	Q16656-4
	NRF1	NM_001040110.2		c.1233C>T	p.Ala411Ala	synonymous	Exon 10 of 11	NP_001035199.1	Q16656-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRF1	ENST00000393232.6	TSL:1 MANE Select	c.1233C>T	p.Ala411Ala	synonymous	Exon 10 of 11	ENSP00000376924.1	Q16656-1
	NRF1	ENST00000311967.6	TSL:1	c.1233C>T	p.Ala411Ala	synonymous	Exon 10 of 12	ENSP00000309826.2	Q16656-4
	NRF1	ENST00000393230.6	TSL:1	c.1233C>T	p.Ala411Ala	synonymous	Exon 10 of 11	ENSP00000376922.2	Q16656-1

Frequencies

GnomAD3 genomes AF: 0.00173 AC: 263 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00235

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00240 AC: 558 AN: 232924 AF XY: 0.00234

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00149

Gnomad ASJ exome AF: 0.00872

Gnomad EAS exome AF: 0.000120

Gnomad FIN exome AF: 0.00103

Gnomad NFE exome AF: 0.00288

Gnomad OTH exome AF: 0.00321

GnomAD4 exome AF: 0.00272 AC: 3915 AN: 1441828 Hom.: 11 Cov.: 30 AF XY: 0.00280 AC XY: 2006 AN XY: 717526

African (AFR) AF: 0.000720 AC: 23 AN: 31940

American (AMR) AF: 0.00163 AC: 61 AN: 37522

Ashkenazi Jewish (ASJ) AF: 0.00990 AC: 251 AN: 25360

East Asian (EAS) AF: 0.0000511 AC: 2 AN: 39166

South Asian (SAS) AF: 0.00239 AC: 198 AN: 82986

European-Finnish (FIN) AF: 0.000847 AC: 45 AN: 53150

Middle Eastern (MID) AF: 0.00736 AC: 42 AN: 5704

European-Non Finnish (NFE) AF: 0.00281 AC: 3111 AN: 1106388

Other (OTH) AF: 0.00305 AC: 182 AN: 59612

GnomAD4 genome AF: 0.00173 AC: 263 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.00153 AC XY: 114 AN XY: 74490

African (AFR) AF: 0.000818 AC: 34 AN: 41578

American (AMR) AF: 0.000980 AC: 15 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00235 AC: 160 AN: 68030

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00278 Hom.: 1

Bravo AF: 0.00209

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		-0.080
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

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: rs149764867; hg19: chr7-129367090;