dbSNP rs3735006: NRF1:p.Asp191Asp (chr7-129690513-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_005011.5(NRF1):c.573C>T(p.Asp191Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 1,614,046 control chromosomes in the GnomAD database, including 2,590 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 0.044 ( 174 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2416 hom. )

Consequence

NRF1
NM_005011.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.14

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=-2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRF1	NM_005011.5 link	c.573C>T	p.Asp191Asp	synonymous_variant	Exon 5 of 11	ENST00000393232.6	NP_005002.3	Q16656-1A0A024R770
NRF1	NM_001293163.2 link	c.573C>T	p.Asp191Asp	synonymous_variant	Exon 5 of 12		NP_001280092.1	Q16656-4A0A024R774
NRF1	NM_001040110.2 link	c.573C>T	p.Asp191Asp	synonymous_variant	Exon 5 of 11		NP_001035199.1	Q16656-1A0A024R770
NRF1	NM_001293164.2 link	c.90C>T	p.Asp30Asp	synonymous_variant	Exon 4 of 10		NP_001280093.1	Q16656-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRF1	ENST00000393232.6 link	c.573C>T	p.Asp191Asp	synonymous_variant	Exon 5 of 11	1	NM_005011.5	ENSP00000376924.1		Q16656-1

Frequencies

GnomAD3 genomes

AF:

0.0441

AC:

6712

AN:

152124

Hom.:

174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.0496

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.0613

Gnomad SAS

AF:

0.0216

Gnomad FIN

AF:

0.0380

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0611

Gnomad OTH

AF:

0.0536

GnomAD2 exomes

AF:

0.0458

AC:

11500

AN:

251230

AF XY:

0.0460

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.0339

Gnomad ASJ exome

AF:

0.0304

Gnomad EAS exome

AF:

0.0589

Gnomad FIN exome

AF:

0.0355

Gnomad NFE exome

AF:

0.0610

Gnomad OTH exome

AF:

0.0545

GnomAD4 exome

AF:

0.0547

AC:

79910

AN:

1461804

Hom.:

2416

Cov.:

AF XY:

0.0539

AC XY:

39171

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.0142

AC:

475

AN:

33478

American (AMR)

AF:

0.0349

AC:

1563

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

845

AN:

26136

East Asian (EAS)

AF:

0.0612

AC:

2429

AN:

39700

South Asian (SAS)

AF:

0.0213

AC:

1837

AN:

86250

European-Finnish (FIN)

AF:

0.0320

AC:

1708

AN:

53418

Middle Eastern (MID)

AF:

0.0843

AC:

486

AN:

5766

European-Non Finnish (NFE)

AF:

0.0607

AC:

67505

AN:

1111938

Other (OTH)

AF:

0.0507

AC:

3062

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

3818

7637

11455

15274

19092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2446

4892

7338

9784

12230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0440

AC:

6706

AN:

152242

Hom.:

174

Cov.:

AF XY:

0.0436

AC XY:

3249

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0162

AC:

671

AN:

41546

American (AMR)

AF:

0.0495

AC:

757

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0279

AC:

AN:

3472

East Asian (EAS)

AF:

0.0614

AC:

318

AN:

5178

South Asian (SAS)

AF:

0.0210

AC:

101

AN:

4816

European-Finnish (FIN)

AF:

0.0380

AC:

403

AN:

10602

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0612

AC:

4160

AN:

68022

Other (OTH)

AF:

0.0531

AC:

112

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

320

640

959

1279

1599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0526

Hom.:

178

Bravo

AF:

0.0440

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.0624

EpiControl

AF:

0.0690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

2.3

(source)

DANN

Benign

0.71

PhyloP100

-2.1

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over