Variant 5-157460465-G-A 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+108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,134,938 control chromosomes in the GnomAD database, including 6,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.078 ( 603 hom., cov: 33)

Exomes 𝑓: 0.10 ( 6042 hom. )

Consequence

NIPAL4
NM_001099287.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.604

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=-0.82).

BP6

Variant 5-157460465-G-A is Benign according to our data. Variant chr5-157460465-G-A is described in ClinVar as [Benign]. Clinvar id is 1286577.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
NIPAL4	NM_001099287.2 linkuse as main transcript	c.37+108G>A	intron_variant	ENST00000311946.8	NP_001092757.2
NIPAL4	NM_001172292.2 linkuse as main transcript	c.37+108G>A	intron_variant		NP_001165763.2
NIPAL4	XM_011534552.2 linkuse as main transcript		upstream_gene_variant		XP_011532854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPAL4	ENST00000311946.8 linkuse as main transcript	c.37+108G>A		intron_variant		1	NM_001099287.2	ENSP00000311687	P1	Q0D2K0-1

Frequencies

GnomAD3 genomes

AF:

0.0775

AC:

11802

AN:

152246

Hom.:

602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0768

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.0275

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.0968

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0997

Gnomad OTH

AF:

0.0769

GnomAD4 exome

AF:

0.105

AC:

102957

AN:

982574

Hom.:

6042

Cov.:

AF XY:

0.109

AC XY:

54324

AN XY:

500602

show subpopulations

Gnomad4 AFR exome

AF:

0.0261

Gnomad4 AMR exome

AF:

0.0736

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.0351

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.0935

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0990

GnomAD4 genome

AF:

0.0775

AC:

11813

AN:

152364

Hom.:

603

Cov.:

AF XY:

0.0794

AC XY:

5916

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0258

Gnomad4 AMR

AF:

0.0769

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.0276

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.0968

Gnomad4 NFE

AF:

0.0997

Gnomad4 OTH

AF:

0.0813

Alfa

AF:

0.0336

Hom.:

Bravo

AF:

0.0722

Asia WGS

AF:

0.123

AC:

427

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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.8

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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