rs10865972

Variant names:

• chr3-52457431-C-A
• rs10865972
• NM_007184.4:c.94-412C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-52457431-C-A
• chr3-52457431-C-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.94-412C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,304 control chromosomes in the GnomAD database, including 67,843 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 0.94 (67843 hom., cov: 34)
• Consequence: NISCH NM_007184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 13 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NISCH	NM_007184.4	MANE Select	c.94-412C>A		intron	N/A	NP_009115.3
	NISCH	NM_001276293.2		c.94-412C>A		intron	N/A	NP_001263222.2
	NISCH	NM_001276294.2		c.94-412C>A		intron	N/A	NP_001263223.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NISCH	ENST00000345716.9	TSL:1 MANE Select	c.94-412C>A		intron	N/A	ENSP00000339958.4
	NISCH	ENST00000479054.5	TSL:1	c.94-412C>A		intron	N/A	ENSP00000418232.1
	NISCH	ENST00000488380.5	TSL:1	c.94-412C>A		intron	N/A	ENSP00000417812.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143599 AN: 152186 Hom.: 67789 Cov.: 34

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.944

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

GnomAD4 genome AF: 0.944 AC: 143712 AN: 152304 Hom.: 67843 Cov.: 34 AF XY: 0.946 AC XY: 70474 AN XY: 74476

African (AFR) AF: 0.953 AC: 39603 AN: 41548

American (AMR) AF: 0.936 AC: 14318 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.966 AC: 3353 AN: 3472

East Asian (EAS) AF: 0.976 AC: 5063 AN: 5186

South Asian (SAS) AF: 0.957 AC: 4618 AN: 4826

European-Finnish (FIN) AF: 0.967 AC: 10266 AN: 10618

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63417 AN: 68030

Other (OTH) AF: 0.943 AC: 1994 AN: 2114

Alfa AF: 0.934 Hom.: 78043

Bravo AF: 0.948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.72
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10865972; hg19: chr3-52491447;