Variant 8-98193384-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001321635.2(NIPAL2):c.1040-294G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,612,268 control chromosomes in the GnomAD database, including 220,036 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 21419 hom., cov: 32)

Exomes 𝑓: 0.52 ( 198617 hom. )

Consequence

NIPAL2
NM_001321635.2 intron

Scores

Splicing: ADA: 0.9991

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

NIPAL2 (HGNC:25854): (NIPA like domain containing 2) Predicted to enable magnesium ion transmembrane transporter activity. Predicted to be involved in magnesium ion transport. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

NIPAL2 links:

NIPAL2-AS1 (HGNC:):

NIPAL2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPAL2	NM_001321635.2 linkuse as main transcript	c.1040-294G>A		intron_variant		ENST00000430223.7	NP_001308564.1
NIPAL2-AS1	XR_928444.3 linkuse as main transcript	n.662+13340C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
NIPAL2	ENST00000430223.7 linkuse as main transcript	c.1040-294G>A	intron_variant	1	NM_001321635.2	ENSP00000407087	P1	Q9H841-2
NIPAL2	ENST00000341166.3 linkuse as main transcript	c.1067+1G>A	splice_donor_variant	2		ENSP00000339256		Q9H841-1
NIPAL2	ENST00000520545.5 linkuse as main transcript	n.1059-294G>A	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80415

AN:

151894

Hom.:

21398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.526

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.601

Gnomad SAS

AF:

0.634

Gnomad FIN

AF:

0.516

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.544

GnomAD3 exomes

AF:

0.542

AC:

136366

AN:

251370

Hom.:

37563

AF XY:

0.542

AC XY:

73653

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.520

Gnomad AMR exome

AF:

0.636

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.593

Gnomad SAS exome

AF:

0.608

Gnomad FIN exome

AF:

0.510

Gnomad NFE exome

AF:

0.496

Gnomad OTH exome

AF:

0.540

GnomAD4 exome

AF:

0.520

AC:

758742

AN:

1460256

Hom.:

198617

Cov.:

AF XY:

0.521

AC XY:

378176

AN XY:

726472

show subpopulations

Gnomad4 AFR exome

AF:

0.524

Gnomad4 AMR exome

AF:

0.636

Gnomad4 ASJ exome

AF:

0.558

Gnomad4 EAS exome

AF:

0.589

Gnomad4 SAS exome

AF:

0.605

Gnomad4 FIN exome

AF:

0.507

Gnomad4 NFE exome

AF:

0.505

Gnomad4 OTH exome

AF:

0.530

GnomAD4 genome

AF:

0.529

AC:

80485

AN:

152012

Hom.:

21419

Cov.:

AF XY:

0.533

AC XY:

39616

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.527

Gnomad4 AMR

AF:

0.595

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.601

Gnomad4 SAS

AF:

0.633

Gnomad4 FIN

AF:

0.516

Gnomad4 NFE

AF:

0.502

Gnomad4 OTH

AF:

0.542

Alfa

AF:

0.509

Hom.:

31560

Bravo

AF:

0.532

TwinsUK

AF:

0.491

AC:

1820

ALSPAC

AF:

0.500

AC:

1928

ESP6500AA

AF:

0.520

AC:

2289

ESP6500EA

AF:

0.509

AC:

4379

ExAC

AF:

0.536

AC:

65127

Asia WGS

AF:

0.624

AC:

2172

AN:

3478

EpiCase

AF:

0.504

EpiControl

AF:

0.504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.62

Eigen

Benign

0.089

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.00094

MutationTaster

Benign

1.0

P;P

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.77

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over