chr3-52459259-A-G

Variant names:

• chr3-52459259-A-G
• rs9855470
• NM_007184.4:c.360+415A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007184.4(NISCH):​c.360+415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 152,280 control chromosomes in the GnomAD database, including 70,644 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.96 (70644 hom., cov: 31)
• Consequence: NISCH NM_007184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NISCH	NM_007184.4	c.360+415A>G		intron_variant	Intron 3 of 20	ENST00000345716.9	NP_009115.3
NISCH	NM_001276293.2	c.360+415A>G		intron_variant	Intron 3 of 12		NP_001263222.2
NISCH	NM_001276294.2	c.360+415A>G		intron_variant	Intron 3 of 13		NP_001263223.2
NISCH	XM_047447373.1	c.360+415A>G		intron_variant	Intron 3 of 17		XP_047303329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NISCH	ENST00000345716.9	c.360+415A>G		intron_variant	Intron 3 of 20	1	NM_007184.4	ENSP00000339958.4

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146511 AN: 152162 Hom.: 70587 Cov.: 31

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.957

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.963 AC: 146627 AN: 152280 Hom.: 70644 Cov.: 31 AF XY: 0.965 AC XY: 71843 AN XY: 74456

African (AFR) AF: 0.990 AC: 41111 AN: 41542

American (AMR) AF: 0.949 AC: 14514 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3368 AN: 3472

East Asian (EAS) AF: 0.979 AC: 5071 AN: 5180

South Asian (SAS) AF: 0.979 AC: 4722 AN: 4822

European-Finnish (FIN) AF: 0.969 AC: 10287 AN: 10614

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64399 AN: 68026

Other (OTH) AF: 0.957 AC: 2025 AN: 2116

Alfa AF: 0.955 Hom.: 8359

Bravo AF: 0.962

Asia WGS AF: 0.962 AC: 3347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.024
DANN	Benign	0.23
PhyloP100		-1.3
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: rs9855470; hg19: chr3-52493275;