Variant rs757388 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080413.3(NOBOX):c.1154+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 1,591,958 control chromosomes in the GnomAD database, including 287,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28921 hom., cov: 33)

Exomes 𝑓: 0.60 ( 258739 hom. )

Consequence

NOBOX
NM_001080413.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.185

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-144399746-A-G is Benign according to our data. Variant chr7-144399746-A-G is described in ClinVar as [Benign]. Clinvar id is 359144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-144399746-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOBOX	NM_001080413.3 linkuse as main transcript	c.1154+11T>C		intron_variant		ENST00000467773.1	NP_001073882.3
NOBOX	XM_017011742.3 linkuse as main transcript	c.1058+11T>C		intron_variant			XP_016867231.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
NOBOX	ENST00000467773.1 linkuse as main transcript	c.1154+11T>C	intron_variant	5	NM_001080413.3	ENSP00000419457		O60393-1
NOBOX	ENST00000483238.5 linkuse as main transcript	c.1058+11T>C	intron_variant	5		ENSP00000419565	A2	O60393-2
NOBOX	ENST00000643164.1 linkuse as main transcript	c.251+11T>C	intron_variant			ENSP00000495343
NOBOX	ENST00000645489.1 linkuse as main transcript	c.803+11T>C	intron_variant			ENSP00000496732	P2

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

93023

AN:

151994

Hom.:

28891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.619

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.829

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.620

GnomAD3 exomes

AF:

0.633

AC:

145869

AN:

230290

Hom.:

47262

AF XY:

0.640

AC XY:

79460

AN XY:

124222

show subpopulations

Gnomad AFR exome

AF:

0.652

Gnomad AMR exome

AF:

0.651

Gnomad ASJ exome

AF:

0.599

Gnomad EAS exome

AF:

0.822

Gnomad SAS exome

AF:

0.803

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.600

GnomAD4 exome

AF:

0.595

AC:

856852

AN:

1439846

Hom.:

258739

Cov.:

AF XY:

0.602

AC XY:

430378

AN XY:

714978

show subpopulations

Gnomad4 AFR exome

AF:

0.646

Gnomad4 AMR exome

AF:

0.646

Gnomad4 ASJ exome

AF:

0.603

Gnomad4 EAS exome

AF:

0.788

Gnomad4 SAS exome

AF:

0.799

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.571

Gnomad4 OTH exome

AF:

0.617

GnomAD4 genome

AF:

0.612

AC:

93105

AN:

152112

Hom.:

28921

Cov.:

AF XY:

0.617

AC XY:

45886

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.645

Gnomad4 AMR

AF:

0.619

Gnomad4 ASJ

AF:

0.606

Gnomad4 EAS

AF:

0.828

Gnomad4 SAS

AF:

0.832

Gnomad4 FIN

AF:

0.538

Gnomad4 NFE

AF:

0.569

Gnomad4 OTH

AF:

0.625

Alfa

AF:

0.599

Hom.:

4695

Bravo

AF:

0.615

Asia WGS

AF:

0.812

AC:

2821

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Premature ovarian failure 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

DANN

Benign

0.66

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