NM_001099287.2:c.37+24C>G

Variant names:

• chr5-157460381-C-G
• rs180845128
• NM_001099287.2:c.37+24C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.13
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099287.2. 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
	NIPAL4	NM_001099287.2	MANE Select	c.37+24C>G		intron	N/A	NP_001092757.2	Q0D2K0-1
	NIPAL4	NM_001172292.2		c.37+24C>G		intron	N/A	NP_001165763.2	Q0D2K0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPAL4	ENST00000311946.8	TSL:1 MANE Select	c.37+24C>G		intron	N/A	ENSP00000311687.8	Q0D2K0-1
	NIPAL4	ENST00000521390.5	TSL:1	n.142+24C>G		intron	N/A
	NIPAL4	ENST00000435489.7	TSL:2	c.37+24C>G		intron	N/A	ENSP00000406456.3	Q0D2K0-2

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2616 AN: 152244 Hom.: 39 Cov.: 33

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

GnomAD2 exomes AF: 0.0232 AC: 3191 AN: 137382 AF XY: 0.0262

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 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.: 30 AF XY: 0.0237 AC XY: 16133 AN XY: 681058

African (AFR) AF: 0.00316 AC: 99 AN: 31342

American (AMR) AF: 0.00501 AC: 178 AN: 35548

Ashkenazi Jewish (ASJ) AF: 0.00760 AC: 190 AN: 24994

East Asian (EAS) AF: 0.000589 AC: 21 AN: 35644

South Asian (SAS) AF: 0.0524 AC: 4133 AN: 78892

European-Finnish (FIN) AF: 0.0531 AC: 2185 AN: 41168

Middle Eastern (MID) AF: 0.0221 AC: 94 AN: 4260

European-Non Finnish (NFE) AF: 0.0217 AC: 23194 AN: 1071156

Other (OTH) AF: 0.0201 AC: 1154 AN: 57386

GnomAD4 genome AF: 0.0171 AC: 2612 AN: 152360 Hom.: 39 Cov.: 33 AF XY: 0.0190 AC XY: 1414 AN XY: 74502

African (AFR) AF: 0.00344 AC: 143 AN: 41592

American (AMR) AF: 0.00712 AC: 109 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0503 AC: 243 AN: 4828

European-Finnish (FIN) AF: 0.0576 AC: 612 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0211 AC: 1434 AN: 68028

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.0189 Hom.: 6

Bravo AF: 0.0119

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.65
PhyloP100		-4.1
PromoterAI		0.057	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs180845128; hg19: chr5-156887389;