rs1024481

Variant names:

• chr7-144410460-G-A
• rs1024481
• NM_001080413.3:c.-233C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080413.3(NOBOX):​c.-233C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,936 control chromosomes in the GnomAD database, including 15,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (15079 hom., cov: 32)
• Consequence: NOBOX NM_001080413.3 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.37
• Publications: 4 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=-0.92).
• BP6: Variant 7-144410460-G-A is Benign according to our data. Variant chr7-144410460-G-A is described in ClinVar as Benign. ClinVar VariationId is 1222264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.-233C>T		upstream_gene_variant		ENST00000467773.1	NP_001073882.3
NOBOX	XM_017011742.3	c.-233C>T		upstream_gene_variant			XP_016867231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOBOX	ENST00000467773.1	c.-233C>T		upstream_gene_variant		5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.-233C>T		upstream_gene_variant		5		ENSP00000419565.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65887 AN: 151818 Hom.: 15073 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.476

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.434 AC: 65929 AN: 151936 Hom.: 15079 Cov.: 32 AF XY: 0.440 AC XY: 32675 AN XY: 74244

African (AFR) AF: 0.425 AC: 17595 AN: 41410

American (AMR) AF: 0.495 AC: 7557 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1740 AN: 3470

East Asian (EAS) AF: 0.815 AC: 4208 AN: 5166

South Asian (SAS) AF: 0.607 AC: 2915 AN: 4804

European-Finnish (FIN) AF: 0.367 AC: 3864 AN: 10540

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26675 AN: 67970

Other (OTH) AF: 0.479 AC: 1011 AN: 2110

Alfa AF: 0.419 Hom.: 61535

Bravo AF: 0.441

Asia WGS AF: 0.673 AC: 2335 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.77
PhyloP100		-1.4
PromoterAI		0.0014	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1024481; hg19: chr7-144107553;