rs727714

Variant names:

• chr7-144401899-G-A
• rs727714
• NM_001080413.3:c.262C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-144401899-G-A
• chr7-144401899-G-C
• chr7-144401899-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001080413.3(NOBOX):​c.262C>T​(p.Leu88Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,609,278 control chromosomes in the GnomAD database, including 290,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28882 hom., cov: 31)
  • Exomes 𝑓: 0.59 (262007 hom.)
• Consequence: NOBOX NM_001080413.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.146
• Publications: 24 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-144401899-G-A is Benign according to our data. Variant chr7-144401899-G-A is described in ClinVar as Benign. ClinVar VariationId is 359152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.146 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.811 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOBOX	NM_001080413.3	MANE Select	c.262C>T	p.Leu88Leu	synonymous	Exon 3 of 10	NP_001073882.3	O60393-1
	NOBOX	NM_001436401.1		c.38-302C>T		intron	N/A	NP_001423330.1	A0A2R8Y8C8
	NOBOX	NM_001436402.1		c.38-1587C>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.262C>T	p.Leu88Leu	synonymous	Exon 3 of 10	ENSP00000419457.1	O60393-1
	NOBOX	ENST00000645489.2		c.38-302C>T		intron	N/A	ENSP00000496732.1
	NOBOX	ENST00000643164.2		c.38-1587C>T		intron	N/A	ENSP00000495343.2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92907 AN: 151814 Hom.: 28852 Cov.: 31

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.620

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: 0.619

GnomAD2 exomes AF: 0.632 AC: 157122 AN: 248510 AF XY: 0.638

Gnomad AFR exome AF: 0.651

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: 0.571

Gnomad OTH exome AF: 0.598

GnomAD4 exome AF: 0.595 AC: 866739 AN: 1457346 Hom.: 262007 Cov.: 33 AF XY: 0.602 AC XY: 436375 AN XY: 725156

African (AFR) AF: 0.646 AC: 21562 AN: 33360

American (AMR) AF: 0.646 AC: 28864 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 15730 AN: 26084

East Asian (EAS) AF: 0.788 AC: 31258 AN: 39680

South Asian (SAS) AF: 0.799 AC: 68756 AN: 86094

European-Finnish (FIN) AF: 0.529 AC: 28212 AN: 53380

Middle Eastern (MID) AF: 0.666 AC: 3834 AN: 5760

European-Non Finnish (NFE) AF: 0.570 AC: 631425 AN: 1108090

Other (OTH) AF: 0.616 AC: 37098 AN: 60214

GnomAD4 genome AF: 0.612 AC: 92989 AN: 151932 Hom.: 28882 Cov.: 31 AF XY: 0.617 AC XY: 45817 AN XY: 74246

African (AFR) AF: 0.644 AC: 26681 AN: 41402

American (AMR) AF: 0.620 AC: 9471 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2099 AN: 3464

East Asian (EAS) AF: 0.829 AC: 4267 AN: 5148

South Asian (SAS) AF: 0.832 AC: 4003 AN: 4810

European-Finnish (FIN) AF: 0.538 AC: 5672 AN: 10544

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

European-Non Finnish (NFE) AF: 0.569 AC: 38673 AN: 67966

Other (OTH) AF: 0.624 AC: 1316 AN: 2110

Alfa AF: 0.579 Hom.: 36593

Bravo AF: 0.615

Asia WGS AF: 0.812 AC: 2821 AN: 3478

EpiCase AF: 0.583

EpiControl AF: 0.586

ClinVar

ClinVar submissions

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	-0.90
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs727714; hg19: chr7-144098992; COSMIC: COSV56196559;