Variant 7-129671445-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.240C>T(p.Ala80=) 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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.550

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NRF1	NM_005011.5 linkuse as main transcript	c.240C>T	p.Ala80=	synonymous_variant	3/11	ENST00000393232.6
NRF1	NM_001293163.2 linkuse as main transcript	c.240C>T	p.Ala80=	synonymous_variant	3/12
NRF1	NM_001040110.2 linkuse as main transcript	c.240C>T	p.Ala80=	synonymous_variant	3/11
NRF1	NM_001293164.2 linkuse as main transcript	c.-145-6187C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRF1	ENST00000393232.6 linkuse as main transcript	c.240C>T	p.Ala80=	synonymous_variant	3/11	1	NM_005011.5	P1	Q16656-1

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

152126

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00158

AC:

395

AN:

250700

Hom.:

AF XY:

0.00156

AC XY:

211

AN XY:

135498

show subpopulations

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 SAS exome

AF:

0.0000328

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.:

Cov.:

AF XY:

0.00269

AC XY:

1955

AN XY:

726652

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00343

Gnomad4 OTH exome

AF:

0.00172

GnomAD4 genome

AF:

0.00176

AC:

268

AN:

152244

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.00298

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00229

Hom.:

Bravo

AF:

0.00165

EpiCase

AF:

0.00235

EpiControl

AF:

0.00225

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.81

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