Variant chr7-129727250-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_005011.5(NRF1):c.1233C>T(p.Ala411=) 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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0800

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NRF1	NM_005011.5 linkuse as main transcript	c.1233C>T	p.Ala411=	synonymous_variant	10/11	ENST00000393232.6
NRF1	NM_001293163.2 linkuse as main transcript	c.1233C>T	p.Ala411=	synonymous_variant	10/12
NRF1	NM_001040110.2 linkuse as main transcript	c.1233C>T	p.Ala411=	synonymous_variant	10/11
NRF1	NM_001293164.2 linkuse as main transcript	c.750C>T	p.Ala250=	synonymous_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRF1	ENST00000393232.6 linkuse as main transcript	c.1233C>T	p.Ala411=	synonymous_variant	10/11	1	NM_005011.5	P1	Q16656-1

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

263

AN:

152224

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00240

AC:

558

AN:

232924

Hom.:

AF XY:

0.00234

AC XY:

297

AN XY:

126916

show subpopulations

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 SAS exome

AF:

0.00199

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.:

Cov.:

AF XY:

0.00280

AC XY:

2006

AN XY:

717526

show subpopulations

Gnomad4 AFR exome

AF:

0.000720

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.00990

Gnomad4 EAS exome

AF:

0.0000511

Gnomad4 SAS exome

AF:

0.00239

Gnomad4 FIN exome

AF:

0.000847

Gnomad4 NFE exome

AF:

0.00281

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.00173

AC:

263

AN:

152342

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00235

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00209

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.59

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over