7-144397625-C-G

Variant names:

• chr7-144397625-C-G
• rs75574842
• NM_001080413.3:c.1775-84G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001080413.3(NOBOX):​c.1775-84G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,210,642 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0041 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (95 hom.)
• Consequence: NOBOX NM_001080413.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0041 (624/152292) while in subpopulation AMR AF= 0.0034 (52/15300). AF 95% confidence interval is 0.00283. There are 9 homozygotes in gnomad4. There are 262 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 624 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.1775-84G>C		intron_variant	Intron 9 of 9	ENST00000467773.1	NP_001073882.3
NOBOX	XM_017011742.3	c.1679-84G>C		intron_variant	Intron 9 of 9		XP_016867231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOBOX	ENST00000467773.1	c.1775-84G>C		intron_variant	Intron 9 of 9	5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.1679-84G>C		intron_variant	Intron 9 of 9	5		ENSP00000419565.1
NOBOX	ENST00000645489.1	c.1424-84G>C		intron_variant	Intron 7 of 7			ENSP00000496732.1
NOBOX	ENST00000643164.1	c.872-84G>C		intron_variant	Intron 6 of 6			ENSP00000495343.1

Frequencies

GnomAD3 genomes AF: 0.00410 AC: 624 AN: 152174 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00317

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.00405 AC: 4284 AN: 1058350 Hom.: 95 AF XY: 0.00411 AC XY: 2145 AN XY: 521786

Gnomad4 AFR exome AF: 0.00240

Gnomad4 AMR exome AF: 0.00326

Gnomad4 ASJ exome AF: 0.0810

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00228

Gnomad4 FIN exome AF: 0.000589

Gnomad4 NFE exome AF: 0.00238

Gnomad4 OTH exome AF: 0.00974

GnomAD4 genome AF: 0.00410 AC: 624 AN: 152292 Hom.: 9 Cov.: 32 AF XY: 0.00352 AC XY: 262 AN XY: 74458

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.0839

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00318

Gnomad4 OTH AF: 0.0123

Bravo AF: 0.00485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.027
DANN	Benign	0.58

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;