rs7168367

Positions:

• chr15-22806332-G-A

Variant summary

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

The ENST00000337435.9(NIPA1):​c.179-4417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,124 control chromosomes in the GnomAD database, including 13,611 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 0.33 (13611 hom., cov: 33)
• Consequence: NIPA1 ENST00000337435.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPA1	NM_144599.5	c.179-4417G>A		intron_variant		ENST00000337435.9	NP_653200.2
NIPA1	NM_001142275.1	c.-47-4417G>A		intron_variant			NP_001135747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPA1	ENST00000337435.9	c.179-4417G>A		intron_variant		1	NM_144599.5	ENSP00000337452	P1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49516 AN: 152006 Hom.: 13579 Cov.: 33

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49591 AN: 152124 Hom.: 13611 Cov.: 33 AF XY: 0.322 AC XY: 23905 AN XY: 74354

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.278

Alfa AF: 0.164 Hom.: 5930

Bravo AF: 0.349

Asia WGS AF: 0.386 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.44

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: rs7168367; hg19: chr15-23066736;