rs117894530

Variant names:

• chr15-22851674-C-T
• rs117894530
• NM_030922.7:c.-58C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-22851674-C-T
• chr15-22851674-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.568
• Publications: 3 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030922.7. 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
	NIPA2	NM_030922.7	MANE Select	c.-58C>T		5_prime_UTR	Exon 4 of 8	NP_112184.4
	NIPA2	NM_001008860.3		c.-58C>T		5_prime_UTR	Exon 3 of 7	NP_001008860.1	Q8N8Q9-1
	NIPA2	NM_001008892.3		c.-58C>T		5_prime_UTR	Exon 2 of 6	NP_001008892.1	Q8N8Q9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA2	ENST00000337451.8	TSL:5 MANE Select	c.-58C>T		5_prime_UTR	Exon 4 of 8	ENSP00000337618.3	Q8N8Q9-1
	NIPA2	ENST00000398013.7	TSL:1	c.-58C>T		5_prime_UTR	Exon 2 of 6	ENSP00000381095.3	Q8N8Q9-1
	NIPA2	ENST00000359727.8	TSL:1	c.-58C>T		5_prime_UTR	Exon 3 of 6	ENSP00000352762.4	Q8N8Q9-2

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2935 AN: 152070 Hom.: 45 Cov.: 32

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.: 17 AF XY: 0.0243 AC XY: 15803 AN XY: 650708

African (AFR) AF: 0.00303 AC: 87 AN: 28718

American (AMR) AF: 0.00760 AC: 234 AN: 30778

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 431 AN: 22678

East Asian (EAS) AF: 0.0000784 AC: 3 AN: 38272

South Asian (SAS) AF: 0.00893 AC: 644 AN: 72098

European-Finnish (FIN) AF: 0.0780 AC: 3991 AN: 51198

Middle Eastern (MID) AF: 0.00744 AC: 39 AN: 5242

European-Non Finnish (NFE) AF: 0.0255 AC: 25513 AN: 1000340

Other (OTH) AF: 0.0220 AC: 1192 AN: 54220

GnomAD4 genome AF: 0.0193 AC: 2935 AN: 152188 Hom.: 45 Cov.: 32 AF XY: 0.0204 AC XY: 1518 AN XY: 74384

African (AFR) AF: 0.00431 AC: 179 AN: 41530

American (AMR) AF: 0.0109 AC: 166 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00871 AC: 42 AN: 4820

European-Finnish (FIN) AF: 0.0734 AC: 777 AN: 10588

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0247 AC: 1680 AN: 68000

Other (OTH) AF: 0.0104 AC: 22 AN: 2106

Alfa AF: 0.0203 Hom.: 8

Bravo AF: 0.0145

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	18
DANN	Benign	0.83
PhyloP100		0.57
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

Other links and lift over

dbSNP: rs117894530; hg19: chr15-23021394;