chr3-52479825-A-G
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2
The NM_007184.4(NISCH):c.1379A>G(p.Lys460Arg) variant causes a missense change. The variant allele was found at a frequency of 0.001 in 1,613,766 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0055 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 9 hom. )
Consequence
NISCH
NM_007184.4 missense
NM_007184.4 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 6.76
Genes affected
NISCH (HGNC:18006): (nischarin) This gene encodes a nonadrenergic imidazoline-1 receptor protein that localizes to the cytosol and anchors to the inner layer of the plasma membrane. The orthologous mouse protein has been shown to influence cytoskeletal organization and cell migration by binding to alpha-5-beta-1 integrin. In humans, this protein has been shown to bind to the adapter insulin receptor substrate 4 (IRS4) to mediate translocation of alpha-5 integrin from the cell membrane to endosomes. Expression of this protein was reduced in human breast cancers while its overexpression reduced tumor growth and metastasis; possibly by limiting the expression of alpha-5 integrin. In human cardiac tissue, this gene was found to affect cell growth and death while in neural tissue it affected neuronal growth and differentiation. Alternative splicing results in multiple transcript variants encoding differerent isoforms. Some isoforms lack the expected C-terminal domains of a functional imidazoline receptor. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, NISCH
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005086541).
BP6
?
Variant 3-52479825-A-G is Benign according to our data. Variant chr3-52479825-A-G is described in ClinVar as [Benign]. Clinvar id is 791926.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00545 (830/152270) while in subpopulation AFR AF= 0.0188 (782/41546). AF 95% confidence interval is 0.0177. There are 6 homozygotes in gnomad4. There are 395 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 827 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NISCH | NM_007184.4 | c.1379A>G | p.Lys460Arg | missense_variant | 12/21 | ENST00000345716.9 | |
NISCH | NM_001276293.2 | c.1379A>G | p.Lys460Arg | missense_variant | 12/13 | ||
NISCH | NM_001276294.2 | c.1379A>G | p.Lys460Arg | missense_variant | 12/14 | ||
NISCH | XM_047447373.1 | c.1379A>G | p.Lys460Arg | missense_variant | 12/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NISCH | ENST00000345716.9 | c.1379A>G | p.Lys460Arg | missense_variant | 12/21 | 1 | NM_007184.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00544 AC: 827AN: 152152Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00130 AC: 326AN: 250582Hom.: 2 AF XY: 0.000849 AC XY: 115AN XY: 135446
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GnomAD4 exome AF: 0.000536 AC: 784AN: 1461496Hom.: 9 Cov.: 31 AF XY: 0.000459 AC XY: 334AN XY: 727004
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191
Asia WGS
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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 | Invitae | May 30, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;N
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
P;P;P;.
Vest4
MVP
MPC
0.85
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at