15-22786298-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000437912.6(NIPA1):c.-48+11985C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,244 control chromosomes in the GnomAD database, including 6,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (6131 hom., cov: 32)
  • Exomes 𝑓: 0.25 (4 hom.)
• Consequence: NIPA1 ENST00000437912.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.742

Genes affected

NIPA1 (HGNC:17043): (NIPA magnesium transporter 1) This gene encodes a magnesium transporter that associates with early endosomes and the cell surface in a variety of neuronal and epithelial cells. This protein may play a role in nervous system development and maintenance. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene have been associated with autosomal dominant spastic paraplegia 6. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-22786298-C-G is Benign according to our data. Variant chr15-22786298-C-G is described in ClinVar as [Benign]. Clinvar id is 679847.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA1	NM_001142275.1	c.-48+50C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA1	ENST00000437912.6	c.-48+11985C>G		intron_variant		1
NIPA1	ENST00000561183.5	c.-48+50C>G		intron_variant		1
NIPA1	ENST00000560069.5	n.31+50C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38273 AN: 151996 Hom.: 6129 Cov.: 32

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.0918

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.246 AC: 32 AN: 130 Hom.: 4 Cov.: 0 AF XY: 0.220 AC XY: 18 AN XY: 82

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.252 AC: 38270 AN: 152114 Hom.: 6131 Cov.: 32 AF XY: 0.251 AC XY: 18699 AN XY: 74366

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.0924

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.280

Alfa AF: 0.305 Hom.: 1057

Bravo AF: 0.232

Asia WGS AF: 0.167 AC: 582 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.2
Dann	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62001112; hg19: chr15-23086770;