rs3735887

chr8-98193384-C-T

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

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-AS1 (HGNC:):

ACMG classification

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	UniProt
NIPAL2	NM_001321635.2	c.1040-294G>A		intron_variant		ENST00000430223.7
NIPAL2-AS1	XR_928444.3	n.662+13340C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPAL2	ENST00000430223.7	c.1040-294G>A		intron_variant		1	NM_001321635.2	P1
NIPAL2	ENST00000341166.3	c.1067+1G>A		splice_donor_variant		2
NIPAL2	ENST00000520545.5	n.1059-294G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80415 AN: 151894 Hom.: 21398 Cov.: 32

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

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.: 41 AF XY: 0.521 AC XY: 378176 AN XY: 726472

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.: 32 AF XY: 0.533 AC XY: 39616 AN XY: 74288

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	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	17
Dann	Benign	0.62
Eigen	Benign	0.089
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.00094	N
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

Other links and lift over

dbSNP: rs3735887; hg19: chr8-99205612; COSMIC: COSV57841589; COSMIC: COSV57841589;