dbSNP rs62001112: NIPA1:c.-48+11985C>G (chr15-22786298-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142275.1(NIPA1):c.-48+50C>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
NM_001142275.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.742

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 6
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

NIPA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142275.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA1	NM_001142275.1		c.-48+50C>G		intron	N/A	NP_001135747.1	Q8TAY1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NIPA1	ENST00000437912.6	TSL:1	c.-48+11985C>G	intron	N/A	ENSP00000393962.2	Q7RTP0-2
NIPA1	ENST00000561183.5	TSL:1	c.-48+50C>G	intron	N/A	ENSP00000453722.1	Q7RTP0-2
NIPA1	ENST00000560069.5	TSL:4	n.31+50C>G	intron	N/A

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

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.278

AC:

AN:

108

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.252

AC:

38270

AN:

152114

Hom.:

6131

Cov.:

AF XY:

0.251

AC XY:

18699

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0661

AC:

2746

AN:

41554

American (AMR)

AF:

0.240

AC:

3668

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1192

AN:

3470

East Asian (EAS)

AF:

0.0924

AC:

476

AN:

5150

South Asian (SAS)

AF:

0.211

AC:

1018

AN:

4820

European-Finnish (FIN)

AF:

0.383

AC:

4060

AN:

10598

Middle Eastern (MID)

AF:

0.312

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.357

AC:

24269

AN:

67926

Other (OTH)

AF:

0.280

AC:

591

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1398

2796

4195

5593

6991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.305

Hom.:

1057

Bravo

AF:

0.232

Asia WGS

AF:

0.167

AC:

582

AN:

3468

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.2

(source)

DANN

Benign

0.31

PhyloP100

-0.74

PromoterAI

0.0090

Neutral

(source)

Splicing

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