rs3764213

chr15-22845401-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA2	NM_030922.7	c.-94+134G>C		intron_variant		ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8	c.-94+134G>C		intron_variant		5	NM_030922.7	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31359 AN: 151930 Hom.: 3488 Cov.: 32

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: 2 AN: 6 Hom.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.206 AC: 31396 AN: 152048 Hom.: 3496 Cov.: 32 AF XY: 0.208 AC XY: 15496 AN XY: 74344

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.216

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.35
Dann	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs3764213; hg19: chr15-23027667;