rs7800847

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080413.3(NOBOX):c.349C>T(p.Arg117Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,515,074 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 122 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 114 hom. )

Consequence

NOBOX
NM_001080413.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:7

Conservation

PhyloP100: 1.28

Publications

18 publications found

Variant links:

Genes affected

NOBOX (HGNC:22448): (NOBOX oogenesis homeobox) This homeobox gene encodes a transcription factor that is thought to play a role in oogenesis. In mice, it is essential for folliculogenesis and regulation of oocyte-specific genes. Defects in this gene result in premature ovarian failure type 5.[provided by RefSeq, May 2011]

NOBOX Gene-Disease associations (from GenCC):

premature ovarian failure 5
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

NOBOX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027316809).

BP6

Variant 7-144401541-G-A is Benign according to our data. Variant chr7-144401541-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 167875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3 link	c.349C>T	p.Arg117Trp	missense_variant	Exon 4 of 10	ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	NM_001436401.1 link	c.94C>T	p.Arg32Trp	missense_variant	Exon 2 of 8		NP_001423330.1
NOBOX	XM_017011742.3 link	c.349C>T	p.Arg117Trp	missense_variant	Exon 4 of 10		XP_016867231.1	O60393-2
NOBOX	NM_001436402.1 link	c.38-1229C>T		intron_variant	Intron 1 of 6		NP_001423331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOBOX	ENST00000467773.1 link	c.349C>T	p.Arg117Trp	missense_variant	Exon 4 of 10	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 link	c.349C>T	p.Arg117Trp	missense_variant	Exon 4 of 10	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 link	c.94C>T	p.Arg32Trp	missense_variant	Exon 2 of 8			ENSP00000496732.1	A0A2R8Y8C8
NOBOX	ENST00000643164.1 link	c.38-1229C>T		intron_variant	Intron 1 of 6			ENSP00000495343.1	A0A2R8Y683

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3362

AN:

152182

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0760

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00968

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.00687

AC:

1144

AN:

166522

AF XY:

0.00514

show subpopulations

Gnomad AFR exome

AF:

0.0766

Gnomad AMR exome

AF:

0.00360

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000284

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00224

AC:

3051

AN:

1362774

Hom.:

114

Cov.:

AF XY:

0.00199

AC XY:

1332

AN XY:

667756

show subpopulations

African (AFR)

AF:

0.0796

AC:

2407

AN:

30232

American (AMR)

AF:

0.00429

AC:

124

AN:

28908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19884

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38970

South Asian (SAS)

AF:

0.000176

AC:

AN:

68236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46114

Middle Eastern (MID)

AF:

0.00659

AC:

AN:

5308

European-Non Finnish (NFE)

AF:

0.000196

AC:

210

AN:

1068928

Other (OTH)

AF:

0.00466

AC:

262

AN:

56194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

160

320

481

641

801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<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:

0.0221

AC:

3364

AN:

152300

Hom.:

122

Cov.:

AF XY:

0.0215

AC XY:

1600

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0758

AC:

3150

AN:

41548

American (AMR)

AF:

0.00967

AC:

148

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68028

Other (OTH)

AF:

0.0175

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

156

313

469

626

782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0120

Hom.:

Bravo

AF:

0.0247

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0587

AC:

203

ESP6500EA

AF:

0.000537

AC:

ExAC

AF:

0.00643

AC:

731

Asia WGS

AF:

0.00578

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Premature ovarian failure 5

Pathogenic:1Benign:2

Feb 10, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 01, 2011

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not specified

Benign:2

Jan 24, 2018

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 05, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Premature ovarian failure 1

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.64

T;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.0

.;N;N

PhyloP100

1.3

PrimateAI

Benign

0.20

PROVEAN

Benign

-2.2

.;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0010

.;D;D

Sift4G

Uncertain

0.020

.;D;D

Polyphen

0.98

.;.;D

Vest4

0.21, 0.17

MVP

0.83

MPC

0.023

ClinPred

0.024

GERP RS

3.5

Varity_R

0.041

gMVP

0.067

Mutation Taster

=92/8

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over