7-144397690-A-G

Variant names:

• chr7-144397690-A-G
• rs1208217
• NM_001080413.3:c.1775-149T>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.1775-149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 668,566 control chromosomes in the GnomAD database, including 117,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27372 hom., cov: 32)
  • Exomes 𝑓: 0.58 (90372 hom.)
• Consequence: NOBOX NM_001080413.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.269
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-144397690-A-G is Benign according to our data. Variant chr7-144397690-A-G is described in ClinVar as [Benign]. Clinvar id is 1248530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.1775-149T>C		intron_variant	Intron 9 of 9	ENST00000467773.1	NP_001073882.3
NOBOX	NM_001436401.1	c.1424-149T>C		intron_variant	Intron 7 of 7		NP_001423330.1
NOBOX	NM_001436402.1	c.872-149T>C		intron_variant	Intron 6 of 6		NP_001423331.1
NOBOX	XM_017011742.3	c.1679-149T>C		intron_variant	Intron 9 of 9		XP_016867231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOBOX	ENST00000467773.1	c.1775-149T>C		intron_variant	Intron 9 of 9	5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.1679-149T>C		intron_variant	Intron 9 of 9	5		ENSP00000419565.1
NOBOX	ENST00000645489.1	c.1424-149T>C		intron_variant	Intron 7 of 7			ENSP00000496732.1
NOBOX	ENST00000643164.1	c.872-149T>C		intron_variant	Intron 6 of 6			ENSP00000495343.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90292 AN: 151890 Hom.: 27335 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.580 AC: 299804 AN: 516558 Hom.: 90372 AF XY: 0.592 AC XY: 157847 AN XY: 266784

African (AFR) AF: 0.634 AC: 8734 AN: 13782

American (AMR) AF: 0.622 AC: 11351 AN: 18258

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 8164 AN: 14056

East Asian (EAS) AF: 0.771 AC: 24091 AN: 31246

South Asian (SAS) AF: 0.795 AC: 33274 AN: 41850

European-Finnish (FIN) AF: 0.501 AC: 14701 AN: 29338

Middle Eastern (MID) AF: 0.661 AC: 1398 AN: 2114

European-Non Finnish (NFE) AF: 0.537 AC: 181454 AN: 337730

Other (OTH) AF: 0.590 AC: 16637 AN: 28184

GnomAD4 genome AF: 0.595 AC: 90384 AN: 152008 Hom.: 27372 Cov.: 32 AF XY: 0.600 AC XY: 44564 AN XY: 74316

African (AFR) AF: 0.635 AC: 26300 AN: 41444

American (AMR) AF: 0.607 AC: 9281 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2033 AN: 3472

East Asian (EAS) AF: 0.821 AC: 4229 AN: 5152

South Asian (SAS) AF: 0.832 AC: 4014 AN: 4826

European-Finnish (FIN) AF: 0.510 AC: 5391 AN: 10570

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.545 AC: 37051 AN: 67950

Other (OTH) AF: 0.611 AC: 1288 AN: 2108

Alfa AF: 0.549 Hom.: 14762

Bravo AF: 0.599

Asia WGS AF: 0.809 AC: 2809 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 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	-0.90
CADD	Benign	0.41
DANN	Benign	0.28
PhyloP100		-0.27
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: rs1208217; hg19: chr7-144094783; COSMIC: COSV99779538;