rs757388

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.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

Publications

12 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=-0.85).

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.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3 link	c.1154+11T>C	intron_variant	Intron 6 of 9	ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	NM_001436401.1 link	c.803+11T>C	intron_variant	Intron 4 of 7		NP_001423330.1
NOBOX	NM_001436402.1 link	c.251+11T>C	intron_variant	Intron 3 of 6		NP_001423331.1
NOBOX	XM_017011742.3 link	c.1058+11T>C	intron_variant	Intron 6 of 9		XP_016867231.1	O60393-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOBOX	ENST00000467773.1 link	c.1154+11T>C	intron_variant	Intron 6 of 9	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 link	c.1058+11T>C	intron_variant	Intron 6 of 9	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 link	c.803+11T>C	intron_variant	Intron 4 of 7			ENSP00000496732.1	A0A2R8Y8C8
NOBOX	ENST00000643164.1 link	c.251+11T>C	intron_variant	Intron 3 of 6			ENSP00000495343.1	A0A2R8Y683

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

GnomAD2 exomes

AF:

0.633

AC:

145869

AN:

230290

AF XY:

0.640

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 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

African (AFR)

AF:

0.646

AC:

21454

AN:

33186

American (AMR)

AF:

0.646

AC:

27660

AN:

42824

Ashkenazi Jewish (ASJ)

AF:

0.603

AC:

15583

AN:

25828

East Asian (EAS)

AF:

0.788

AC:

30999

AN:

39356

South Asian (SAS)

AF:

0.799

AC:

66841

AN:

83700

European-Finnish (FIN)

AF:

0.528

AC:

27858

AN:

52728

Middle Eastern (MID)

AF:

0.666

AC:

3816

AN:

5732

European-Non Finnish (NFE)

AF:

0.571

AC:

625873

AN:

1096886

Other (OTH)

AF:

0.617

AC:

36768

AN:

59606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

17422

34845

52267

69690

87112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.612

AC:

93105

AN:

152112

Hom.:

28921

Cov.:

AF XY:

0.617

AC XY:

45886

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.645

AC:

26750

AN:

41482

American (AMR)

AF:

0.619

AC:

9475

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2102

AN:

3468

East Asian (EAS)

AF:

0.828

AC:

4283

AN:

5170

South Asian (SAS)

AF:

0.832

AC:

4013

AN:

4824

European-Finnish (FIN)

AF:

0.538

AC:

5689

AN:

10572

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38668

AN:

67982

Other (OTH)

AF:

0.625

AC:

1319

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1845

3689

5534

7378

9223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: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). 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

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

-0.85

CADD

Benign

4.5

(source)

DANN

Benign

0.66

PhyloP100

0.18

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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rs757388

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