rs757388

Variant names:

• chr7-144399746-A-G
• rs757388
• NM_001080413.3:c.1154+11T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-144399746-A-G
• chr7-144399746-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080413.3(NOBOX):​c.1154+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 1,591,958 control chromosomes in the GnomAD database, including 287,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28921 hom., cov: 33)
  • Exomes 𝑓: 0.60 (258739 hom.)
• Consequence: NOBOX NM_001080413.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.185
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-144399746-A-G is Benign according to our data. Variant chr7-144399746-A-G is described in ClinVar as Benign. ClinVar VariationId is 359144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOBOX	NM_001080413.3	MANE Select	c.1154+11T>C		intron	N/A	NP_001073882.3
	NOBOX	NM_001436401.1		c.803+11T>C		intron	N/A	NP_001423330.1
	NOBOX	NM_001436402.1		c.251+11T>C		intron	N/A	NP_001423331.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOBOX	ENST00000467773.1	TSL:5 MANE Select	c.1154+11T>C		intron	N/A	ENSP00000419457.1
	NOBOX	ENST00000483238.5	TSL:5	c.1058+11T>C		intron	N/A	ENSP00000419565.1
	NOBOX	ENST00000645489.1		c.803+11T>C		intron	N/A	ENSP00000496732.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 93023 AN: 151994 Hom.: 28891 Cov.: 33

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.620

GnomAD2 exomes AF: 0.633 AC: 145869 AN: 230290 AF XY: 0.640

Gnomad AFR exome AF: 0.652

Gnomad AMR exome AF: 0.651

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.822

Gnomad FIN exome AF: 0.533

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.600

GnomAD4 exome AF: 0.595 AC: 856852 AN: 1439846 Hom.: 258739 Cov.: 30 AF XY: 0.602 AC XY: 430378 AN XY: 714978

African (AFR) AF: 0.646 AC: 21454 AN: 33186

American (AMR) AF: 0.646 AC: 27660 AN: 42824

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 15583 AN: 25828

East Asian (EAS) AF: 0.788 AC: 30999 AN: 39356

South Asian (SAS) AF: 0.799 AC: 66841 AN: 83700

European-Finnish (FIN) AF: 0.528 AC: 27858 AN: 52728

Middle Eastern (MID) AF: 0.666 AC: 3816 AN: 5732

European-Non Finnish (NFE) AF: 0.571 AC: 625873 AN: 1096886

Other (OTH) AF: 0.617 AC: 36768 AN: 59606

GnomAD4 genome AF: 0.612 AC: 93105 AN: 152112 Hom.: 28921 Cov.: 33 AF XY: 0.617 AC XY: 45886 AN XY: 74358

African (AFR) AF: 0.645 AC: 26750 AN: 41482

American (AMR) AF: 0.619 AC: 9475 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2102 AN: 3468

East Asian (EAS) AF: 0.828 AC: 4283 AN: 5170

South Asian (SAS) AF: 0.832 AC: 4013 AN: 4824

European-Finnish (FIN) AF: 0.538 AC: 5689 AN: 10572

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38668 AN: 67982

Other (OTH) AF: 0.625 AC: 1319 AN: 2112

Alfa AF: 0.599 Hom.: 4695

Bravo AF: 0.615

Asia WGS AF: 0.812 AC: 2821 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Premature ovarian failure 5 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.66
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs757388; hg19: chr7-144096839; COSMIC: COSV107299525;