Genetic Variant ENST00000437912.6:c.-48+11985C>G (chr15-22786298-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.742

Variant links:

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]

NIPA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
NIPA1	NM_001142275.1 link	c.-48+50C>G		intron_variant	Intron 1 of 4		NP_001135747.1	Q7RTP0-2A0A024R344Q8TAY1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
NIPA1	ENST00000437912.6 link	c.-48+11985C>G	intron_variant	Intron 1 of 4	1	ENSP00000393962.2	Q7RTP0-2
NIPA1	ENST00000561183.5 link	c.-48+50C>G	intron_variant	Intron 1 of 4	1	ENSP00000453722.1	Q7RTP0-2
NIPA1	ENST00000560069.5 link	n.31+50C>G	intron_variant	Intron 1 of 6	4

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38273

AN:

151996

Hom.:

6129

Cov.:

show subpopulations

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:

AN:

130

Hom.:

Cov.:

AF XY:

0.220

AC XY:

AN XY:

show subpopulations

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.:

AF XY:

0.251

AC XY:

18699

AN XY:

74366

show subpopulations

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: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

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over