Variant 7-129657492-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005011.5(NRF1):c.141T>G(p.Ser47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,613,256 control chromosomes in the GnomAD database, including 101,771 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 0.42 ( 15725 hom., cov: 31)

Exomes 𝑓: 0.33 ( 86046 hom. )

Consequence

NRF1
NM_005011.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Variant links:

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]

NRF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=-1.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NRF1	NM_005011.5 linkuse as main transcript	c.141T>G	p.Ser47=	synonymous_variant	2/11	ENST00000393232.6
NRF1	NM_001293163.2 linkuse as main transcript	c.141T>G	p.Ser47=	synonymous_variant	2/12
NRF1	NM_001040110.2 linkuse as main transcript	c.141T>G	p.Ser47=	synonymous_variant	2/11
NRF1	NM_001293164.2 linkuse as main transcript	c.-228T>G		5_prime_UTR_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRF1	ENST00000393232.6 linkuse as main transcript	c.141T>G	p.Ser47=	synonymous_variant	2/11	1	NM_005011.5	P1	Q16656-1

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63850

AN:

151700

Hom.:

15694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.678

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.368

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.370

GnomAD3 exomes

AF:

0.381

AC:

95731

AN:

251434

Hom.:

20431

AF XY:

0.376

AC XY:

51088

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.634

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.311

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.337

GnomAD4 exome

AF:

0.331

AC:

483127

AN:

1461440

Hom.:

86046

Cov.:

AF XY:

0.333

AC XY:

242021

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.692

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.223

Gnomad4 EAS exome

AF:

0.615

Gnomad4 SAS exome

AF:

0.475

Gnomad4 FIN exome

AF:

0.312

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.421

AC:

63928

AN:

151816

Hom.:

15725

Cov.:

AF XY:

0.424

AC XY:

31441

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.677

Gnomad4 AMR

AF:

0.368

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.608

Gnomad4 SAS

AF:

0.468

Gnomad4 FIN

AF:

0.315

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.374

Alfa

AF:

0.307

Hom.:

17048

Bravo

AF:

0.435

Asia WGS

AF:

0.542

AC:

1885

AN:

3478

EpiCase

AF:

0.289

EpiControl

AF:

0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.2

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over