rs1208179

Variant names:

• chr7-144410186-A-G
• rs1208179
• NM_001080413.3:c.42T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-144410186-A-G
• chr7-144410186-A-C

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.42T>C​(p.Gly14Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,569,332 control chromosomes in the GnomAD database, including 21,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1562 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19819 hom.)
• Consequence: NOBOX NM_001080413.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.32
• Publications: 11 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=-0.93).
• BP6: Variant 7-144410186-A-G is Benign according to our data. Variant chr7-144410186-A-G is described in ClinVar as Benign. ClinVar VariationId is 138536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 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.42T>C	p.Gly14Gly	synonymous	Exon 1 of 10	NP_001073882.3	O60393-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOBOX	ENST00000467773.1	TSL:5 MANE Select	c.42T>C	p.Gly14Gly	synonymous	Exon 1 of 10	ENSP00000419457.1	O60393-1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19607 AN: 151878 Hom.: 1563 Cov.: 33

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.147 AC: 27214 AN: 185426 AF XY: 0.154

Gnomad AFR exome AF: 0.0567

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.00904

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.162 AC: 229509 AN: 1417336 Hom.: 19819 Cov.: 30 AF XY: 0.164 AC XY: 115188 AN XY: 700508

African (AFR) AF: 0.0591 AC: 1929 AN: 32644

American (AMR) AF: 0.128 AC: 4941 AN: 38472

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2900 AN: 25368

East Asian (EAS) AF: 0.0104 AC: 396 AN: 37902

South Asian (SAS) AF: 0.224 AC: 17975 AN: 80370

European-Finnish (FIN) AF: 0.164 AC: 8290 AN: 50696

Middle Eastern (MID) AF: 0.168 AC: 959 AN: 5712

European-Non Finnish (NFE) AF: 0.169 AC: 183340 AN: 1087416

Other (OTH) AF: 0.149 AC: 8779 AN: 58756

GnomAD4 genome AF: 0.129 AC: 19622 AN: 151996 Hom.: 1562 Cov.: 33 AF XY: 0.130 AC XY: 9639 AN XY: 74270

African (AFR) AF: 0.0613 AC: 2540 AN: 41432

American (AMR) AF: 0.105 AC: 1611 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3472

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5172

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4814

European-Finnish (FIN) AF: 0.174 AC: 1832 AN: 10550

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11581 AN: 67970

Other (OTH) AF: 0.115 AC: 243 AN: 2112

Alfa AF: 0.149 Hom.: 1216

Bravo AF: 0.118

Asia WGS AF: 0.130 AC: 454 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.42
PhyloP100		-2.3
PromoterAI		0.030	Neutral
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: rs1208179; hg19: chr7-144107279; COSMIC: COSV71989190;