Variant chr7-144398264-C-T details in Genebe, Genetics Data Aggregator

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

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]

NOBOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

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

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

High AC in GnomAd4 at 677 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOBOX	NM_001080413.3 linkuse as main transcript	c.1774+18G>A		intron_variant		ENST00000467773.1	NP_001073882.3	O60393-1
NOBOX	XM_017011742.3 linkuse as main transcript	c.1678+18G>A		intron_variant			XP_016867231.1	O60393-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
NOBOX	ENST00000467773.1 linkuse as main transcript	c.1774+18G>A	intron_variant	5	NM_001080413.3	ENSP00000419457.1	O60393-1
NOBOX	ENST00000483238.5 linkuse as main transcript	c.1678+18G>A	intron_variant	5		ENSP00000419565.1	O60393-2
NOBOX	ENST00000645489.1 linkuse as main transcript	c.1423+18G>A	intron_variant			ENSP00000496732.1	A0A2R8Y8C8
NOBOX	ENST00000643164.1 linkuse as main transcript	c.871+18G>A	intron_variant			ENSP00000495343.1	A0A2R8Y683

Frequencies

GnomAD3 genomes

AF:

0.00444

AC:

676

AN:

152230

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00444

AC:

677

AN:

152348

Hom.:

Cov.:

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.:

Bravo

AF:

0.00508

Asia WGS

AF:

0.000866

AC:

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 submitter

clinical testing

GeneDx

Nov 13, 2017

This 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.

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