7-144398264-C-T

Variant names:

• chr7-144398264-C-T
• rs142147025
• NM_001080413.3:c.1774+18G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001080413.3(NOBOX):​c.1774+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,536,502 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (29 hom.)
• Consequence: NOBOX NM_001080413.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-144398264-C-T is Benign according to our data. Variant chr7-144398264-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 381954.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00444 (677/152348) while in subpopulation AMR AF = 0.00993 (152/15314). AF 95% confidence interval is 0.00864. There are 3 homozygotes in GnomAd4. There are 298 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 677 AD gene.

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.1774+18G>A		intron	N/A	NP_001073882.3	O60393-1
	NOBOX	NM_001436401.1		c.1423+18G>A		intron	N/A	NP_001423330.1	A0A2R8Y8C8
	NOBOX	NM_001436402.1		c.871+18G>A		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.1774+18G>A		intron	N/A	ENSP00000419457.1	O60393-1
	NOBOX	ENST00000645489.2		c.1423+18G>A		intron	N/A	ENSP00000496732.1
	NOBOX	ENST00000643164.2		c.871+18G>A		intron	N/A	ENSP00000495343.2

Frequencies

GnomAD3 genomes AF: 0.00444 AC: 676 AN: 152230 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.00994

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00589

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00413 AC: 585 AN: 141660 AF XY: 0.00403

Gnomad AFR exome AF: 0.000659

Gnomad AMR exome AF: 0.00688

Gnomad ASJ exome AF: 0.00381

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00160

Gnomad NFE exome AF: 0.00592

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00595 AC: 8234 AN: 1384154 Hom.: 29 Cov.: 31 AF XY: 0.00586 AC XY: 4002 AN XY: 683036

African (AFR) AF: 0.000887 AC: 28 AN: 31580

American (AMR) AF: 0.00751 AC: 268 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00353 AC: 89 AN: 25178

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35732

South Asian (SAS) AF: 0.000468 AC: 37 AN: 79086

European-Finnish (FIN) AF: 0.00223 AC: 78 AN: 35014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5496

European-Non Finnish (NFE) AF: 0.00692 AC: 7467 AN: 1078488

Other (OTH) AF: 0.00458 AC: 265 AN: 57882

GnomAD4 genome AF: 0.00444 AC: 677 AN: 152348 Hom.: 3 Cov.: 32 AF XY: 0.00400 AC XY: 298 AN XY: 74494

African (AFR) AF: 0.000745 AC: 31 AN: 41584

American (AMR) AF: 0.00993 AC: 152 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00282 AC: 30 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00589 AC: 401 AN: 68038

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00218 Hom.: 0

Bravo AF: 0.00508

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.49
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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: rs142147025; hg19: chr7-144095357;