Variant 5-157460381-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001099287.2(NIPAL4):c.37+24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,532,750 control chromosomes in the GnomAD database, including 558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 39 hom., cov: 33)

Exomes 𝑓: 0.023 ( 519 hom. )

Consequence

NIPAL4
NM_001099287.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.13

Variant links:

Genes affected

NIPAL4 (HGNC:28018): (NIPA like domain containing 4) This gene likely encodes a membrane receptor. Mutations in this gene have been associated with autosomal recessive congenital ichthyosis. [provided by RefSeq, Feb 2010]

NIPAL4 links:

ADAM19 (HGNC:197): (ADAM metallopeptidase domain 19) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This member is a type I transmembrane protein and serves as a marker for dendritic cell differentiation. It has been demonstrated to be an active metalloproteinase, which may be involved in normal physiological processes such as cell migration, cell adhesion, cell-cell and cell-matrix interactions, and signal transduction. It is proposed to play a role in pathological processes, such as cancer, inflammatory diseases, renal diseases, and Alzheimer's disease. [provided by RefSeq, May 2013]

ADAM19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-157460381-C-G is Benign according to our data. Variant chr5-157460381-C-G is described in ClinVar as [Benign]. Clinvar id is 1276105.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPAL4	NM_001099287.2 linkuse as main transcript	c.37+24C>G		intron_variant		ENST00000311946.8
NIPAL4	NM_001172292.2 linkuse as main transcript	c.37+24C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPAL4	ENST00000311946.8 linkuse as main transcript	c.37+24C>G		intron_variant		1	NM_001099287.2	P1	Q0D2K0-1

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2616

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0509

Gnomad FIN

AF:

0.0576

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0232

AC:

3191

AN:

137382

Hom.:

AF XY:

0.0262

AC XY:

1954

AN XY:

74690

show subpopulations

Gnomad AFR exome

AF:

0.00344

Gnomad AMR exome

AF:

0.00472

Gnomad ASJ exome

AF:

0.00761

Gnomad EAS exome

AF:

0.000667

Gnomad SAS exome

AF:

0.0553

Gnomad FIN exome

AF:

0.0582

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.0163

GnomAD4 exome

AF:

0.0226

AC:

31248

AN:

1380390

Hom.:

519

Cov.:

AF XY:

0.0237

AC XY:

16133

AN XY:

681058

show subpopulations

Gnomad4 AFR exome

AF:

0.00316

Gnomad4 AMR exome

AF:

0.00501

Gnomad4 ASJ exome

AF:

0.00760

Gnomad4 EAS exome

AF:

0.000589

Gnomad4 SAS exome

AF:

0.0524

Gnomad4 FIN exome

AF:

0.0531

Gnomad4 NFE exome

AF:

0.0217

Gnomad4 OTH exome

AF:

0.0201

GnomAD4 genome

AF:

0.0171

AC:

2612

AN:

152360

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1414

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00344

Gnomad4 AMR

AF:

0.00712

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0503

Gnomad4 FIN

AF:

0.0576

Gnomad4 NFE

AF:

0.0211

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.0189

Hom.:

Bravo

AF:

0.0119

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

0.13

Dann

Benign

0.65

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over