7-144397690-A-G

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.1775-149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 668,566 control chromosomes in the GnomAD database, including 117,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (27372 hom., cov: 32)
  • Exomes 𝑓: 0.58 (90372 hom.)
• Consequence: NOBOX NM_001080413.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.269

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 7-144397690-A-G is Benign according to our data. Variant chr7-144397690-A-G is described in ClinVar as [Benign]. Clinvar id is 1248530.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
NOBOX	NM_001080413.3	c.1775-149T>C		intron_variant		ENST00000467773.1
NOBOX	XM_017011742.3	c.1679-149T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOBOX	ENST00000467773.1	c.1775-149T>C		intron_variant		5	NM_001080413.3
NOBOX	ENST00000483238.5	c.1679-149T>C		intron_variant		5		A2
NOBOX	ENST00000643164.1	c.872-149T>C		intron_variant
NOBOX	ENST00000645489.1	c.1424-149T>C		intron_variant				P2

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90292 AN: 151890 Hom.: 27335 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.580 AC: 299804 AN: 516558 Hom.: 90372 AF XY: 0.592 AC XY: 157847 AN XY: 266784

Gnomad4 AFR exome AF: 0.634

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.771

Gnomad4 SAS exome AF: 0.795

Gnomad4 FIN exome AF: 0.501

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.595 AC: 90384 AN: 152008 Hom.: 27372 Cov.: 32 AF XY: 0.600 AC XY: 44564 AN XY: 74316

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.611

Alfa AF: 0.540 Hom.: 8098

Bravo AF: 0.599

Asia WGS AF: 0.809 AC: 2809 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

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.41
Dann	Benign	0.28

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: rs1208217; hg19: chr7-144094783;