rs6860507

Variant names:

• chr5-157471682-A-G
• rs6860507
• NM_001099287.2:c.451A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-157471682-A-G
• chr5-157471682-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001099287.2(NIPAL4):​c.451A>G​(p.Arg151Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,605,988 control chromosomes in the GnomAD database, including 186,372 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R151R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.48 (17426 hom., cov: 31)
  • Exomes 𝑓: 0.48 (168946 hom.)
• Consequence: NIPAL4 NM_001099287.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.01
• Publications: 30 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.1832983E-6).
• BP6: Variant 5-157471682-A-G is Benign according to our data. Variant chr5-157471682-A-G is described in ClinVar as Benign. ClinVar VariationId is 257436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 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.451A>G	p.Arg151Gly	missense	Exon 5 of 6	NP_001092757.2	Q0D2K0-1
	NIPAL4	NM_001172292.2		c.394A>G	p.Arg132Gly	missense	Exon 4 of 5	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.451A>G	p.Arg151Gly	missense	Exon 5 of 6	ENSP00000311687.8	Q0D2K0-1
	NIPAL4	ENST00000435489.7	TSL:2	c.394A>G	p.Arg132Gly	missense	Exon 4 of 5	ENSP00000406456.3	Q0D2K0-2
	NIPAL4	ENST00000519150.1	TSL:5	n.*150A>G		non_coding_transcript_exon	Exon 6 of 7	ENSP00000430810.1	H0YC31

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72122 AN: 151724 Hom.: 17415 Cov.: 31

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.479

GnomAD2 exomes AF: 0.496 AC: 118724 AN: 239242 AF XY: 0.491

Gnomad AFR exome AF: 0.419

Gnomad AMR exome AF: 0.492

Gnomad ASJ exome AF: 0.541

Gnomad EAS exome AF: 0.738

Gnomad FIN exome AF: 0.487

Gnomad NFE exome AF: 0.487

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.479 AC: 696737 AN: 1454146 Hom.: 168946 Cov.: 35 AF XY: 0.478 AC XY: 345107 AN XY: 722530

African (AFR) AF: 0.413 AC: 13784 AN: 33372

American (AMR) AF: 0.494 AC: 21612 AN: 43760

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 13978 AN: 25970

East Asian (EAS) AF: 0.701 AC: 27745 AN: 39576

South Asian (SAS) AF: 0.420 AC: 35552 AN: 84738

European-Finnish (FIN) AF: 0.489 AC: 25919 AN: 53012

Middle Eastern (MID) AF: 0.505 AC: 2845 AN: 5632

European-Non Finnish (NFE) AF: 0.475 AC: 526489 AN: 1107974

Other (OTH) AF: 0.479 AC: 28813 AN: 60112

GnomAD4 genome AF: 0.475 AC: 72179 AN: 151842 Hom.: 17426 Cov.: 31 AF XY: 0.478 AC XY: 35457 AN XY: 74204

African (AFR) AF: 0.420 AC: 17399 AN: 41400

American (AMR) AF: 0.494 AC: 7530 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1862 AN: 3468

East Asian (EAS) AF: 0.730 AC: 3758 AN: 5146

South Asian (SAS) AF: 0.426 AC: 2050 AN: 4810

European-Finnish (FIN) AF: 0.494 AC: 5208 AN: 10532

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32764 AN: 67924

Other (OTH) AF: 0.479 AC: 1011 AN: 2110

Alfa AF: 0.483 Hom.: 57722

Bravo AF: 0.471

ESP6500AA AF: 0.417 AC: 1701

ESP6500EA AF: 0.465 AC: 3906

ExAC AF: 0.486 AC: 58781

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Autosomal recessive congenital ichthyosis 6 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.81
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0000072	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.0	N
PhyloP100		2.0
PrimateAI	Benign	0.44	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.13
Sift	Benign	0.66	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.092
MPC		0.35
ClinPred		0.00097	T
GERP RS		4.8
Varity_R		0.26
gMVP		0.42
Mutation Taster		=91/9	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: rs6860507; hg19: chr5-156898690; COSMIC: COSV107341057; COSMIC: COSV107341057;