7-144397625-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001080413.3(NOBOX):c.1775-84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,210,516 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (13 hom., cov: 32)
  • Exomes 𝑓: 0.015 (141 hom.)
• Consequence: NOBOX NM_001080413.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.487

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=-0.95).
• BP6: Variant 7-144397625-C-T is Benign according to our data. Variant chr7-144397625-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1201840.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.011 (1673/152284) while in subpopulation NFE AF= 0.0168 (1145/68018). AF 95% confidence interval is 0.016. There are 13 homozygotes in gnomad4. There are 788 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1676 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOBOX	NM_001080413.3	c.1775-84G>A		intron_variant		ENST00000467773.1
NOBOX	XM_017011742.3	c.1679-84G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOBOX	ENST00000467773.1	c.1775-84G>A		intron_variant		5	NM_001080413.3
NOBOX	ENST00000483238.5	c.1679-84G>A		intron_variant		5		A2
NOBOX	ENST00000643164.1	c.872-84G>A		intron_variant
NOBOX	ENST00000645489.1	c.1424-84G>A		intron_variant				P2

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1676 AN: 152166 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00338

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.0154 AC: 16317 AN: 1058232 Hom.: 141 AF XY: 0.0150 AC XY: 7832 AN XY: 521720

Gnomad4 AFR exome AF: 0.00256

Gnomad4 AMR exome AF: 0.00992

Gnomad4 ASJ exome AF: 0.0221

Gnomad4 EAS exome AF: 0.0000591

Gnomad4 SAS exome AF: 0.00974

Gnomad4 FIN exome AF: 0.00851

Gnomad4 NFE exome AF: 0.0171

Gnomad4 OTH exome AF: 0.0146

GnomAD4 genome AF: 0.0110 AC: 1673 AN: 152284 Hom.: 13 Cov.: 32 AF XY: 0.0106 AC XY: 788 AN XY: 74452

Gnomad4 AFR AF: 0.00337

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.0168

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00900 Hom.: 1

Bravo AF: 0.0113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.060
Dann	Benign	0.69

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

Other links and lift over

dbSNP: rs75574842; hg19: chr7-144094718;