dbSNP rs11769847: NOBOX:c.1155-23G>A (chr7-144399505-C-T) – ACMG Classification: Benign (-20 pts)

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.1155-23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,547,152 control chromosomes in the GnomAD database, including 278,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28922 hom., cov: 33)

Exomes 𝑓: 0.59 ( 249868 hom. )

Consequence

NOBOX
NM_001080413.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.00

Publications

9 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 (BayesDel_noAF=-0.84).

BP6

Variant 7-144399505-C-T is Benign according to our data. Variant chr7-144399505-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080413.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOBOX	NM_001080413.3	MANE Select	c.1155-23G>A	intron	N/A	NP_001073882.3	O60393-1
NOBOX	NM_001436401.1		c.804-23G>A	intron	N/A	NP_001423330.1	A0A2R8Y8C8
NOBOX	NM_001436402.1		c.252-23G>A	intron	N/A	NP_001423331.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOBOX	ENST00000467773.1	TSL:5 MANE Select	c.1155-23G>A	intron	N/A	ENSP00000419457.1	O60393-1
NOBOX	ENST00000645489.2		c.804-23G>A	intron	N/A	ENSP00000496732.1
NOBOX	ENST00000643164.2		c.252-23G>A	intron	N/A	ENSP00000495343.2

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

93007

AN:

151964

Hom.:

28892

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.656

Gnomad AMR

AF:

0.620

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.829

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.618

GnomAD2 exomes

AF:

0.639

AC:

106092

AN:

165984

AF XY:

0.648

show subpopulations

Gnomad AFR exome

AF:

0.656

Gnomad AMR exome

AF:

0.650

Gnomad ASJ exome

AF:

0.599

Gnomad EAS exome

AF:

0.821

Gnomad FIN exome

AF:

0.535

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.607

GnomAD4 exome

AF:

0.594

AC:

828797

AN:

1395070

Hom.:

249868

Cov.:

AF XY:

0.601

AC XY:

414465

AN XY:

689716

show subpopulations

African (AFR)

AF:

0.646

AC:

20570

AN:

31840

American (AMR)

AF:

0.643

AC:

23306

AN:

36226

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

15179

AN:

25146

East Asian (EAS)

AF:

0.786

AC:

28630

AN:

36446

South Asian (SAS)

AF:

0.798

AC:

63278

AN:

79344

European-Finnish (FIN)

AF:

0.528

AC:

26399

AN:

49996

Middle Eastern (MID)

AF:

0.666

AC:

3761

AN:

5648

European-Non Finnish (NFE)

AF:

0.571

AC:

611815

AN:

1072404

Other (OTH)

AF:

0.618

AC:

35859

AN:

58020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

16470

32940

49409

65879

82349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17246

34492

51738

68984

86230

<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:

0.612

AC:

93089

AN:

152082

Hom.:

28922

Cov.:

AF XY:

0.617

AC XY:

45871

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.645

AC:

26754

AN:

41498

American (AMR)

AF:

0.620

AC:

9469

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2103

AN:

3470

East Asian (EAS)

AF:

0.828

AC:

4272

AN:

5158

South Asian (SAS)

AF:

0.832

AC:

4015

AN:

4824

European-Finnish (FIN)

AF:

0.539

AC:

5707

AN:

10582

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38647

AN:

67952

Other (OTH)

AF:

0.623

AC:

1316

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1819

3637

5456

7274

9093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.599

Hom.:

4684

Bravo

AF:

0.615

Asia WGS

AF:

0.812

AC:

2821

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Premature ovarian failure 5 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.46

(source)

DANN

Benign

0.63

PhyloP100

-2.0

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over