Genetic Variant NIPA2:c.139+85C>T (chr15-22851955-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030922.7(NIPA2):c.139+85C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,127,056 control chromosomes in the GnomAD database, including 165,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16792 hom., cov: 32)

Exomes 𝑓: 0.54 ( 149069 hom. )

Consequence

NIPA2
NM_030922.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.380

Publications

15 publications found

Variant links:

Genes affected

NIPA2 (HGNC:17044): (NIPA magnesium transporter 2) This gene encodes a possible magnesium transporter. This gene is located adjacent to the imprinted domain in the Prader-Willi syndrome deletion region of chromosome 15. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 7 and 21.[provided by RefSeq, May 2010]

NIPA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-22851955-C-T is Benign according to our data. Variant chr15-22851955-C-T is described in ClinVar as [Benign]. Clinvar id is 1245853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7 link	c.139+85C>T		intron_variant	Intron 4 of 7	ENST00000337451.8	NP_112184.4	Q8N8Q9-1A0A024R372

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA2	ENST00000337451.8 link	c.139+85C>T		intron_variant	Intron 4 of 7	5	NM_030922.7	ENSP00000337618.3		Q8N8Q9-1

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66754

AN:

151902

Hom.:

16795

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.531

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.372

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.432

GnomAD4 exome

AF:

0.544

AC:

530334

AN:

975036

Hom.:

149069

AF XY:

0.544

AC XY:

269824

AN XY:

495614

show subpopulations

African (AFR)

AF:

0.183

AC:

4110

AN:

22408

American (AMR)

AF:

0.457

AC:

12998

AN:

28416

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

7405

AN:

18670

East Asian (EAS)

AF:

0.266

AC:

9743

AN:

36596

South Asian (SAS)

AF:

0.537

AC:

32670

AN:

60850

European-Finnish (FIN)

AF:

0.656

AC:

31688

AN:

48324

Middle Eastern (MID)

AF:

0.398

AC:

1739

AN:

4372

European-Non Finnish (NFE)

AF:

0.573

AC:

407966

AN:

711956

Other (OTH)

AF:

0.507

AC:

22015

AN:

43444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

11452

22905

34357

45810

57262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.439

AC:

66746

AN:

152020

Hom.:

16792

Cov.:

AF XY:

0.442

AC XY:

32862

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.191

AC:

7924

AN:

41478

American (AMR)

AF:

0.439

AC:

6708

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1368

AN:

3472

East Asian (EAS)

AF:

0.280

AC:

1449

AN:

5174

South Asian (SAS)

AF:

0.530

AC:

2552

AN:

4816

European-Finnish (FIN)

AF:

0.660

AC:

6963

AN:

10552

Middle Eastern (MID)

AF:

0.376

AC:

109

AN:

290

European-Non Finnish (NFE)

AF:

0.563

AC:

38236

AN:

67950

Other (OTH)

AF:

0.428

AC:

902

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1733

3466

5199

6932

8665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.508

Hom.:

69795

Bravo

AF:

0.415

Asia WGS

AF:

0.354

AC:

1229

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 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

-0.83

CADD

Benign

6.8

(source)

DANN

Benign

0.70

PhyloP100

-0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

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15-22851955-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over