7-144398637-C-T

Variant names:

• chr7-144398637-C-T
• rs11979528
• NM_001080413.3:c.1470-51G>A

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.1470-51G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,320,932 control chromosomes in the GnomAD database, including 114,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14094 hom., cov: 29)
  • Exomes 𝑓: 0.40 (100248 hom.)
• Consequence: NOBOX NM_001080413.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.615
• Publications: 3 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 7-144398637-C-T is Benign according to our data. Variant chr7-144398637-C-T is described in ClinVar as [Benign]. Clinvar id is 1226872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.1470-51G>A		intron_variant	Intron 8 of 9	ENST00000467773.1	NP_001073882.3
NOBOX	NM_001436401.1	c.1119-51G>A		intron_variant	Intron 6 of 7		NP_001423330.1
NOBOX	NM_001436402.1	c.567-51G>A		intron_variant	Intron 5 of 6		NP_001423331.1
NOBOX	XM_017011742.3	c.1374-51G>A		intron_variant	Intron 8 of 9		XP_016867231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOBOX	ENST00000467773.1	c.1470-51G>A		intron_variant	Intron 8 of 9	5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.1374-51G>A		intron_variant	Intron 8 of 9	5		ENSP00000419565.1
NOBOX	ENST00000645489.1	c.1119-51G>A		intron_variant	Intron 6 of 7			ENSP00000496732.1
NOBOX	ENST00000643164.1	c.567-51G>A		intron_variant	Intron 5 of 6			ENSP00000495343.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63285 AN: 151326 Hom.: 14089 Cov.: 29

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.402 AC: 470567 AN: 1169488 Hom.: 100248 AF XY: 0.409 AC XY: 239585 AN XY: 585692

African (AFR) AF: 0.409 AC: 11275 AN: 27590

American (AMR) AF: 0.489 AC: 17216 AN: 35182

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 10938 AN: 23428

East Asian (EAS) AF: 0.773 AC: 26711 AN: 34538

South Asian (SAS) AF: 0.568 AC: 42091 AN: 74094

European-Finnish (FIN) AF: 0.350 AC: 12131 AN: 34670

Middle Eastern (MID) AF: 0.488 AC: 1783 AN: 3652

European-Non Finnish (NFE) AF: 0.369 AC: 326737 AN: 885948

Other (OTH) AF: 0.430 AC: 21685 AN: 50386

GnomAD4 genome AF: 0.418 AC: 63326 AN: 151444 Hom.: 14094 Cov.: 29 AF XY: 0.425 AC XY: 31418 AN XY: 73960

African (AFR) AF: 0.411 AC: 16954 AN: 41234

American (AMR) AF: 0.480 AC: 7307 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3466

East Asian (EAS) AF: 0.819 AC: 4189 AN: 5114

South Asian (SAS) AF: 0.600 AC: 2875 AN: 4788

European-Finnish (FIN) AF: 0.351 AC: 3696 AN: 10530

Middle Eastern (MID) AF: 0.514 AC: 149 AN: 290

European-Non Finnish (NFE) AF: 0.373 AC: 25319 AN: 67790

Other (OTH) AF: 0.460 AC: 967 AN: 2100

Alfa AF: 0.382 Hom.: 1420

Bravo AF: 0.425

Asia WGS AF: 0.669 AC: 2322 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

- -

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	-0.90
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-0.61
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: rs11979528; hg19: chr7-144095730; COSMIC: COSV56195148;