rs7800847

Variant names:

• chr7-144401541-G-A
• rs7800847
• NM_001080413.3:c.349C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-144401541-G-A
• chr7-144401541-G-C

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.349C>T​(p.Arg117Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,515,074 control chromosomes in the GnomAD database, including 236 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (122 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (114 hom.)
• Consequence: NOBOX NM_001080413.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:8
• Conservation: PhyloP100: 1.28
• Publications: 18 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 (MetaRNN=0.0027316809).
• BP6: Variant 7-144401541-G-A is Benign according to our data. Variant chr7-144401541-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 167875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0736 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.349C>T	p.Arg117Trp	missense	Exon 4 of 10	NP_001073882.3	O60393-1
	NOBOX	NM_001436401.1		c.94C>T	p.Arg32Trp	missense	Exon 2 of 8	NP_001423330.1	A0A2R8Y8C8
	NOBOX	NM_001436402.1		c.38-1229C>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.349C>T	p.Arg117Trp	missense	Exon 4 of 10	ENSP00000419457.1	O60393-1
	NOBOX	ENST00000645489.2		c.94C>T	p.Arg32Trp	missense	Exon 2 of 8	ENSP00000496732.1
	NOBOX	ENST00000643164.2		c.38-1229C>T		intron	N/A	ENSP00000495343.2

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3362 AN: 152182 Hom.: 122 Cov.: 33

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00968

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00687 AC: 1144 AN: 166522 AF XY: 0.00514

Gnomad AFR exome AF: 0.0766

Gnomad AMR exome AF: 0.00360

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000284

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00224 AC: 3051 AN: 1362774 Hom.: 114 Cov.: 31 AF XY: 0.00199 AC XY: 1332 AN XY: 667756

African (AFR) AF: 0.0796 AC: 2407 AN: 30232

American (AMR) AF: 0.00429 AC: 124 AN: 28908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19884

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38970

South Asian (SAS) AF: 0.000176 AC: 12 AN: 68236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46114

Middle Eastern (MID) AF: 0.00659 AC: 35 AN: 5308

European-Non Finnish (NFE) AF: 0.000196 AC: 210 AN: 1068928

Other (OTH) AF: 0.00466 AC: 262 AN: 56194

GnomAD4 genome AF: 0.0221 AC: 3364 AN: 152300 Hom.: 122 Cov.: 33 AF XY: 0.0215 AC XY: 1600 AN XY: 74478

African (AFR) AF: 0.0758 AC: 3150 AN: 41548

American (AMR) AF: 0.00967 AC: 148 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68028

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.0120 Hom.: 27

Bravo AF: 0.0247

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0587 AC: 203

ESP6500EA AF: 0.000537 AC: 4

ExAC AF: 0.00643 AC: 731

Asia WGS AF: 0.00578 AC: 21 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
1	-	2	Premature ovarian failure 5 (3)
-	-	2	not provided (2)
-	-	1	Premature ovarian failure 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.020	D
Polyphen		0.98	D
Vest4		0.21
MVP		0.83
MPC		0.023
ClinPred		0.024	T
GERP RS		3.5
Varity_R		0.041
gMVP		0.067
Mutation Taster		=92/8	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: rs7800847; hg19: chr7-144098634; COSMIC: COSV56194325;