7-129671445-C-T

Variant names:

• chr7-129671445-C-T
• rs146404476
• NM_005011.5:c.240C>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.240C>T​(p.Ala80Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,612,690 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (5 hom.)
• Consequence: NRF1 NM_005011.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.550
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 7-129671445-C-T is Benign according to our data. Variant chr7-129671445-C-T is described in ClinVar as Benign. ClinVar VariationId is 779428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.55 with no splicing effect.
• BS2: High AC in GnomAd4 at 268 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.240C>T	p.Ala80Ala	synonymous	Exon 3 of 11	NP_005002.3
	NRF1	NM_001293163.2		c.240C>T	p.Ala80Ala	synonymous	Exon 3 of 12	NP_001280092.1	Q16656-4
	NRF1	NM_001040110.2		c.240C>T	p.Ala80Ala	synonymous	Exon 3 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.240C>T	p.Ala80Ala	synonymous	Exon 3 of 11	ENSP00000376924.1	Q16656-1
	NRF1	ENST00000311967.6	TSL:1	c.240C>T	p.Ala80Ala	synonymous	Exon 3 of 12	ENSP00000309826.2	Q16656-4
	NRF1	ENST00000393230.6	TSL:1	c.240C>T	p.Ala80Ala	synonymous	Exon 3 of 11	ENSP00000376922.2	Q16656-1

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 268 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00298

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00158 AC: 395 AN: 250700 AF XY: 0.00156

Gnomad AFR exome AF: 0.000866

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00106

Gnomad NFE exome AF: 0.00261

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00280 AC: 4092 AN: 1460446 Hom.: 5 Cov.: 29 AF XY: 0.00269 AC XY: 1955 AN XY: 726652

African (AFR) AF: 0.000717 AC: 24 AN: 33460

American (AMR) AF: 0.00157 AC: 70 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86222

European-Finnish (FIN) AF: 0.00112 AC: 60 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00343 AC: 3815 AN: 1110716

Other (OTH) AF: 0.00172 AC: 104 AN: 60340

GnomAD4 genome AF: 0.00176 AC: 268 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74448

African (AFR) AF: 0.000626 AC: 26 AN: 41536

American (AMR) AF: 0.00196 AC: 30 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000849 AC: 9 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00298 AC: 203 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00229 Hom.: 0

Bravo AF: 0.00165

EpiCase AF: 0.00235

EpiControl AF: 0.00225

ClinVar

ClinVar submissions as Germline

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	-0.26
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.55
Mutation Taster		=96/4	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: rs146404476; hg19: chr7-129311285;