15-22858272-C-T

Variant names:

• chr15-22858272-C-T
• rs4778392
• NM_030922.7:c.197-268C>T

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.197-268C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,102 control chromosomes in the GnomAD database, including 58,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.87 (58396 hom., cov: 33)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.18
• Publications: 0 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=-1.01).
• BP6: Variant 15-22858272-C-T is Benign according to our data. Variant chr15-22858272-C-T is described in ClinVar as [Benign]. Clinvar id is 1279074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7	c.197-268C>T		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.197-268C>T		intron_variant	Intron 5 of 7	5	NM_030922.7	ENSP00000337618.3

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132787 AN: 151984 Hom.: 58335 Cov.: 33

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.874 AC: 132908 AN: 152102 Hom.: 58396 Cov.: 33 AF XY: 0.878 AC XY: 65288 AN XY: 74326

African (AFR) AF: 0.964 AC: 40005 AN: 41500

American (AMR) AF: 0.883 AC: 13498 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2689 AN: 3468

East Asian (EAS) AF: 0.929 AC: 4800 AN: 5166

South Asian (SAS) AF: 0.910 AC: 4385 AN: 4820

European-Finnish (FIN) AF: 0.886 AC: 9383 AN: 10586

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55294 AN: 67968

Other (OTH) AF: 0.863 AC: 1822 AN: 2112

Alfa AF: 0.839 Hom.: 6687

Bravo AF: 0.877

Asia WGS AF: 0.906 AC: 3147 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

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	0.44
DANN	Benign	0.58
PhyloP100		-2.2

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: rs4778392; hg19: chr15-23014796;