chr15-22858257-A-G

Variant names:

• chr15-22858257-A-G
• rs4778391
• NM_030922.7:c.197-283A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030922.7(NIPA2):​c.197-283A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,896 control chromosomes in the GnomAD database, including 16,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (16706 hom., cov: 32)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.939
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 15-22858257-A-G is Benign according to our data. Variant chr15-22858257-A-G is described in ClinVar as [Benign]. Clinvar id is 1178664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7	c.197-283A>G		intron_variant	Intron 5 of 7	ENST00000337451.8	NP_112184.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA2	ENST00000337451.8	c.197-283A>G		intron_variant	Intron 5 of 7	5	NM_030922.7	ENSP00000337618.3

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64331 AN: 151778 Hom.: 16667 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.424 AC: 64427 AN: 151896 Hom.: 16706 Cov.: 32 AF XY: 0.425 AC XY: 31576 AN XY: 74218

African (AFR) AF: 0.713 AC: 29553 AN: 41448

American (AMR) AF: 0.445 AC: 6787 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3466

East Asian (EAS) AF: 0.653 AC: 3352 AN: 5130

South Asian (SAS) AF: 0.382 AC: 1839 AN: 4812

European-Finnish (FIN) AF: 0.233 AC: 2465 AN: 10598

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.262 AC: 17805 AN: 67872

Other (OTH) AF: 0.432 AC: 909 AN: 2102

Alfa AF: 0.345 Hom.: 1332

Bravo AF: 0.449

Asia WGS AF: 0.545 AC: 1893 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.34
PhyloP100		-0.94

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

Other links and lift over

dbSNP: rs4778391; hg19: chr15-23014811;