chr7-144397625-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• premature ovarian failure 5

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 624 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080413.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOBOX	NM_001080413.3	MANE Select	c.1775-84G>C		intron	N/A	NP_001073882.3	O60393-1
	NOBOX	NM_001436401.1		c.1424-84G>C		intron	N/A	NP_001423330.1	A0A2R8Y8C8
	NOBOX	NM_001436402.1		c.872-84G>C		intron	N/A	NP_001423331.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOBOX	ENST00000467773.1	TSL:5 MANE Select	c.1775-84G>C		intron	N/A	ENSP00000419457.1	O60393-1
	NOBOX	ENST00000645489.2		c.1424-84G>C		intron	N/A	ENSP00000496732.1
	NOBOX	ENST00000643164.2		c.872-84G>C		intron	N/A	ENSP00000495343.2

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

African (AFR) AF: 0.00240 AC: 58 AN: 24198

American (AMR) AF: 0.00326 AC: 70 AN: 21482

Ashkenazi Jewish (ASJ) AF: 0.0810 AC: 1435 AN: 17722

East Asian (EAS) AF: 0.00 AC: 0 AN: 33846

South Asian (SAS) AF: 0.00228 AC: 132 AN: 57896

European-Finnish (FIN) AF: 0.000589 AC: 18 AN: 30544

Middle Eastern (MID) AF: 0.0484 AC: 168 AN: 3474

European-Non Finnish (NFE) AF: 0.00238 AC: 1956 AN: 823290

Other (OTH) AF: 0.00974 AC: 447 AN: 45898

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

African (AFR) AF: 0.000481 AC: 20 AN: 41566

American (AMR) AF: 0.00340 AC: 52 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00318 AC: 216 AN: 68024

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00 Hom.: 5

Bravo AF: 0.00485

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.027
DANN	Benign	0.58
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs75574842; hg19: chr7-144094718;