chr7-144397625-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080413.3(NOBOX):​c.1775-84G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000945 in 1,058,378 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: NOBOX NM_001080413.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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>T		intron	N/A	NP_001073882.3	O60393-1
	NOBOX	NM_001436401.1		c.1424-84G>T		intron	N/A	NP_001423330.1	A0A2R8Y8C8
	NOBOX	NM_001436402.1		c.872-84G>T		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>T		intron	N/A	ENSP00000419457.1	O60393-1
	NOBOX	ENST00000645489.2		c.1424-84G>T		intron	N/A	ENSP00000496732.1
	NOBOX	ENST00000643164.2		c.872-84G>T		intron	N/A	ENSP00000495343.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.45e-7 AC: 1 AN: 1058378 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 521798

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24198

American (AMR) AF: 0.00 AC: 0 AN: 21482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17728

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 57894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3476

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 823308

Other (OTH) AF: 0.00 AC: 0 AN: 45904

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.026
DANN	Benign	0.63
PhyloP100		-0.49

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;