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GeneBe

7-144398264-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001080413.3(NOBOX):c.1774+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,536,502 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0059 ( 29 hom. )

Consequence

NOBOX
NM_001080413.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-144398264-C-T is Benign according to our data. Variant chr7-144398264-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 381954.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00444 (677/152348) while in subpopulation AMR AF= 0.00993 (152/15314). AF 95% confidence interval is 0.00864. There are 3 homozygotes in gnomad4. There are 298 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 676 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NOBOXNM_001080413.3 linkuse as main transcriptc.1774+18G>A intron_variant ENST00000467773.1
NOBOXXM_017011742.3 linkuse as main transcriptc.1678+18G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NOBOXENST00000467773.1 linkuse as main transcriptc.1774+18G>A intron_variant 5 NM_001080413.3 O60393-1
NOBOXENST00000483238.5 linkuse as main transcriptc.1678+18G>A intron_variant 5 A2O60393-2
NOBOXENST00000643164.1 linkuse as main transcriptc.871+18G>A intron_variant
NOBOXENST00000645489.1 linkuse as main transcriptc.1423+18G>A intron_variant P2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00444
AC:
676
AN:
152230
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000748
Gnomad AMI
AF:
0.0285
Gnomad AMR
AF:
0.00994
Gnomad ASJ
AF:
0.00403
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00282
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00589
Gnomad OTH
AF:
0.0100
GnomAD3 exomes
AF:
0.00413
AC:
585
AN:
141660
Hom.:
2
AF XY:
0.00403
AC XY:
306
AN XY:
75884
show subpopulations
Gnomad AFR exome
AF:
0.000659
Gnomad AMR exome
AF:
0.00688
Gnomad ASJ exome
AF:
0.00381
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000440
Gnomad FIN exome
AF:
0.00160
Gnomad NFE exome
AF:
0.00592
Gnomad OTH exome
AF:
0.00539
GnomAD4 exome
AF:
0.00595
AC:
8234
AN:
1384154
Hom.:
29
Cov.:
31
AF XY:
0.00586
AC XY:
4002
AN XY:
683036
show subpopulations
Gnomad4 AFR exome
AF:
0.000887
Gnomad4 AMR exome
AF:
0.00751
Gnomad4 ASJ exome
AF:
0.00353
Gnomad4 EAS exome
AF:
0.0000560
Gnomad4 SAS exome
AF:
0.000468
Gnomad4 FIN exome
AF:
0.00223
Gnomad4 NFE exome
AF:
0.00692
Gnomad4 OTH exome
AF:
0.00458
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00444
AC:
677
AN:
152348
Hom.:
3
Cov.:
32
AF XY:
0.00400
AC XY:
298
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.000745
Gnomad4 AMR
AF:
0.00993
Gnomad4 ASJ
AF:
0.00403
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00282
Gnomad4 NFE
AF:
0.00589
Gnomad4 OTH
AF:
0.00993
Alfa
AF:
0.00218
Hom.:
0
Bravo
AF:
0.00508
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 13, 2017This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
0.26
Dann
Benign
0.49

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.

Other links and lift over

dbSNP: rs142147025; hg19: chr7-144095357; API