3-52479011-G-C

Variant names:

• chr3-52479011-G-C
• rs9867823
• NM_007184.4:c.1302+434G>C

Variant summary

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

The NM_007184.4(NISCH):​c.1302+434G>C 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 152,274 control chromosomes in the GnomAD database, including 70,623 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 (70623 hom., cov: 31)
• Consequence: NISCH NM_007184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007184.4. 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
	NISCH	NM_007184.4	MANE Select	c.1302+434G>C		intron	N/A	NP_009115.3	Q9Y2I1-1
	NISCH	NM_001276293.2		c.1302+434G>C		intron	N/A	NP_001263222.2	C9J715
	NISCH	NM_001276294.2		c.1302+434G>C		intron	N/A	NP_001263223.2	Q9Y2I1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NISCH	ENST00000345716.9	TSL:1 MANE Select	c.1302+434G>C		intron	N/A	ENSP00000339958.4	Q9Y2I1-1
	NISCH	ENST00000479054.5	TSL:1	c.1302+434G>C		intron	N/A	ENSP00000418232.1	Q9Y2I1-1
	NISCH	ENST00000488380.5	TSL:1	c.1302+434G>C		intron	N/A	ENSP00000417812.1	C9J715

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146487 AN: 152156 Hom.: 70563 Cov.: 31

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.962

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: 146606 AN: 152274 Hom.: 70623 Cov.: 31 AF XY: 0.965 AC XY: 71818 AN XY: 74446

African (AFR) AF: 0.990 AC: 41137 AN: 41556

American (AMR) AF: 0.946 AC: 14476 AN: 15298

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

East Asian (EAS) AF: 0.979 AC: 5059 AN: 5168

South Asian (SAS) AF: 0.979 AC: 4727 AN: 4826

European-Finnish (FIN) AF: 0.969 AC: 10288 AN: 10614

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64398 AN: 68020

Other (OTH) AF: 0.956 AC: 2022 AN: 2114

Alfa AF: 0.960 Hom.: 8718

Bravo AF: 0.962

Asia WGS AF: 0.966 AC: 3359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.39
PhyloP100		-1.1
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: rs9867823; hg19: chr3-52513027;