7-144397690-A-T

Variant names:

• chr7-144397690-A-T
• rs1208217
• NM_001080413.3:c.1775-149T>A

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.1775-149T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOBOX NM_001080413.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 4 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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.1775-149T>A		intron_variant	Intron 9 of 9	ENST00000467773.1	NP_001073882.3
NOBOX	NM_001436401.1	c.1424-149T>A		intron_variant	Intron 7 of 7		NP_001423330.1
NOBOX	NM_001436402.1	c.872-149T>A		intron_variant	Intron 6 of 6		NP_001423331.1
NOBOX	XM_017011742.3	c.1679-149T>A		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.1775-149T>A		intron_variant	Intron 9 of 9	5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.1679-149T>A		intron_variant	Intron 9 of 9	5		ENSP00000419565.1
NOBOX	ENST00000645489.1	c.1424-149T>A		intron_variant	Intron 7 of 7			ENSP00000496732.1
NOBOX	ENST00000643164.1	c.872-149T>A		intron_variant	Intron 6 of 6			ENSP00000495343.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 517484 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 267228

African (AFR) AF: 0.00 AC: 0 AN: 13798

American (AMR) AF: 0.00 AC: 0 AN: 18276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14072

East Asian (EAS) AF: 0.00 AC: 0 AN: 31262

South Asian (SAS) AF: 0.00 AC: 0 AN: 41934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2116

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 338412

Other (OTH) AF: 0.00 AC: 0 AN: 28230

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.50
PhyloP100		-0.27

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: rs1208217; hg19: chr7-144094783;