Genetic Variant NM_030922.7:c.-94+134G>C (chr15-22845401-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030922.7(NIPA2):c.-94+134G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,048 control chromosomes in the GnomAD database, including 3,496 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3496 hom., cov: 32)

Exomes 𝑓: 0.33 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NIPA2
NM_030922.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.678

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030922.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NIPA2	NM_030922.7	MANE Select	c.-94+134G>C	intron	N/A	NP_112184.4
NIPA2	NM_001008860.3		c.-94+5611G>C	intron	N/A	NP_001008860.1
NIPA2	NM_001008892.3		c.-93-6238G>C	intron	N/A	NP_001008892.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NIPA2	ENST00000337451.8	TSL:5 MANE Select	c.-94+134G>C	intron	N/A	ENSP00000337618.3
NIPA2	ENST00000398013.7	TSL:1	c.-93-6238G>C	intron	N/A	ENSP00000381095.3
NIPA2	ENST00000359727.8	TSL:1	c.-94+134G>C	intron	N/A	ENSP00000352762.4

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31359

AN:

151930

Hom.:

3488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.217

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.333

AC:

AN:

Hom.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.206

AC:

31396

AN:

152048

Hom.:

3496

Cov.:

AF XY:

0.208

AC XY:

15496

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.229

AC:

9511

AN:

41456

American (AMR)

AF:

0.310

AC:

4723

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

784

AN:

3472

East Asian (EAS)

AF:

0.252

AC:

1304

AN:

5184

South Asian (SAS)

AF:

0.196

AC:

944

AN:

4814

European-Finnish (FIN)

AF:

0.158

AC:

1669

AN:

10570

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11829

AN:

67978

Other (OTH)

AF:

0.216

AC:

457

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1254

2507

3761

5014

6268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.108

Hom.:

148

Bravo

AF:

0.217

Asia WGS

AF:

0.224

AC:

779

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.35

(source)

DANN

Benign

0.59

PhyloP100

-0.68

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over