chr15-22858272-C-T

Position:

• chr15-22858272-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NIPA2	NM_030922.7	c.197-268C>T		intron_variant		ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8	c.197-268C>T		intron_variant		5	NM_030922.7	P1

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

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.910

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.863

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs4778392; hg19: chr15-23014796;