Variant chr15-22851674-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030922.7(NIPA2):c.-58C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 1,455,732 control chromosomes in the GnomAD database, including 590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 45 hom., cov: 32)

Exomes 𝑓: 0.025 ( 545 hom. )

Consequence

NIPA2
NM_030922.7 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.568

Variant links:

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]

NIPA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-22851674-C-T is Benign according to our data. Variant chr15-22851674-C-T is described in ClinVar as [Benign]. Clinvar id is 1248113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0193 (2935/152188) while in subpopulation NFE AF= 0.0247 (1680/68000). AF 95% confidence interval is 0.0237. There are 45 homozygotes in gnomad4. There are 1518 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA2	NM_030922.7 linkuse as main transcript	c.-58C>T		5_prime_UTR_variant	4/8	ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8 linkuse as main transcript	c.-58C>T		5_prime_UTR_variant	4/8	5	NM_030922.7	P1	Q8N8Q9-1

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2935

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00850

Gnomad FIN

AF:

0.0734

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0247

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.0247

AC:

32134

AN:

1303544

Hom.:

545

Cov.:

AF XY:

0.0243

AC XY:

15803

AN XY:

650708

show subpopulations

Gnomad4 AFR exome

AF:

0.00303

Gnomad4 AMR exome

AF:

0.00760

Gnomad4 ASJ exome

AF:

0.0190

Gnomad4 EAS exome

AF:

0.0000784

Gnomad4 SAS exome

AF:

0.00893

Gnomad4 FIN exome

AF:

0.0780

Gnomad4 NFE exome

AF:

0.0255

Gnomad4 OTH exome

AF:

0.0220

GnomAD4 genome

AF:

0.0193

AC:

2935

AN:

152188

Hom.:

Cov.:

AF XY:

0.0204

AC XY:

1518

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00431

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00871

Gnomad4 FIN

AF:

0.0734

Gnomad4 NFE

AF:

0.0247

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0203

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

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