7-144398637-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080413.3(NOBOX):c.1470-51G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,320,932 control chromosomes in the GnomAD database, including 114,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (14094 hom., cov: 29)
  • Exomes 𝑓: 0.40 (100248 hom.)
• Consequence: NOBOX NM_001080413.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.615

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-144398637-C-T is Benign according to our data. Variant chr7-144398637-C-T is described in ClinVar as [Benign]. Clinvar id is 1226872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOBOX	NM_001080413.3	c.1470-51G>A		intron_variant		ENST00000467773.1
NOBOX	XM_017011742.3	c.1374-51G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOBOX	ENST00000467773.1	c.1470-51G>A		intron_variant		5	NM_001080413.3
NOBOX	ENST00000483238.5	c.1374-51G>A		intron_variant		5		A2
NOBOX	ENST00000643164.1	c.567-51G>A		intron_variant
NOBOX	ENST00000645489.1	c.1119-51G>A		intron_variant				P2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63285 AN: 151326 Hom.: 14089 Cov.: 29

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.402 AC: 470567 AN: 1169488 Hom.: 100248 AF XY: 0.409 AC XY: 239585 AN XY: 585692

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.773

Gnomad4 SAS exome AF: 0.568

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.418 AC: 63326 AN: 151444 Hom.: 14094 Cov.: 29 AF XY: 0.425 AC XY: 31418 AN XY: 73960

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.460

Alfa AF: 0.382 Hom.: 1420

Bravo AF: 0.425

Asia WGS AF: 0.669 AC: 2322 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.7
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs11979528; hg19: chr7-144095730; COSMIC: COSV56195148;