7-144397549-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001080413.3(NOBOX):c.1775-8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,509,682 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 10 hom. )

Consequence

NOBOX
NM_001080413.3 splice_region, intron

Scores

Splicing: ADA: 0.001858

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0610

Publications

0 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=-0.86).

BP6

Variant 7-144397549-G-T is Benign according to our data. Variant chr7-144397549-G-T is described in ClinVar as [Benign]. Clinvar id is 716086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00635 (968/152358) while in subpopulation AFR AF = 0.022 (914/41596). AF 95% confidence interval is 0.0208. There are 10 homozygotes in GnomAd4. There are 458 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 968 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3 link	c.1775-8C>A	splice_region_variant, intron_variant	Intron 9 of 9	ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	NM_001436401.1 link	c.1424-8C>A	splice_region_variant, intron_variant	Intron 7 of 7		NP_001423330.1
NOBOX	NM_001436402.1 link	c.872-8C>A	splice_region_variant, intron_variant	Intron 6 of 6		NP_001423331.1
NOBOX	XM_017011742.3 link	c.1679-8C>A	splice_region_variant, intron_variant	Intron 9 of 9		XP_016867231.1	O60393-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOBOX	ENST00000467773.1 link	c.1775-8C>A	splice_region_variant, intron_variant	Intron 9 of 9	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 link	c.1679-8C>A	splice_region_variant, intron_variant	Intron 9 of 9	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 link	c.1424-8C>A	splice_region_variant, intron_variant	Intron 7 of 7			ENSP00000496732.1	A0A2R8Y8C8
NOBOX	ENST00000643164.1 link	c.872-8C>A	splice_region_variant, intron_variant	Intron 6 of 6			ENSP00000495343.1	A0A2R8Y683

Frequencies

GnomAD3 genomes

AF:

0.00635

AC:

966

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00161

AC:

191

AN:

118784

AF XY:

0.00129

show subpopulations

Gnomad AFR exome

AF:

0.0240

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000630

Gnomad OTH exome

AF:

0.000284

GnomAD4 exome

AF:

0.000626

AC:

850

AN:

1357324

Hom.:

Cov.:

AF XY:

0.000528

AC XY:

352

AN XY:

666336

show subpopulations

African (AFR)

AF:

0.0231

AC:

711

AN:

30832

American (AMR)

AF:

0.00107

AC:

AN:

32850

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23366

East Asian (EAS)

AF:

0.00

AC:

AN:

35372

South Asian (SAS)

AF:

0.0000662

AC:

AN:

75582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34008

Middle Eastern (MID)

AF:

0.00109

AC:

AN:

5512

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

1063240

Other (OTH)

AF:

0.00136

AC:

AN:

56562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00635

AC:

968

AN:

152358

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

458

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0220

AC:

914

AN:

41596

American (AMR)

AF:

0.00235

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68028

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00385

Hom.:

Bravo

AF:

0.00706

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Premature ovarian failure 5

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.0

(source)

DANN

Benign

0.61

PhyloP100

0.061

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0019

dbscSNV1_RF

Benign

0.046

SpliceAI score (max)

0.11

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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7-144397549-G-T

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