chr3-52457431-C-A

Position:

• chr3-52457431-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NISCH	NM_007184.4	c.94-412C>A		intron_variant		ENST00000345716.9
NISCH	NM_001276293.2	c.94-412C>A		intron_variant
NISCH	NM_001276294.2	c.94-412C>A		intron_variant
NISCH	XM_047447373.1	c.94-412C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NISCH	ENST00000345716.9	c.94-412C>A		intron_variant		1	NM_007184.4
NISCH	ENST00000479054.5	c.94-412C>A		intron_variant		1
NISCH	ENST00000488380.5	c.94-412C>A		intron_variant		1
NISCH	ENST00000420808.2	c.94-412C>A		intron_variant		5		P1

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

Gnomad4 AFR AF: 0.953

Gnomad4 AMR AF: 0.936

Gnomad4 ASJ AF: 0.966

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.932

Gnomad4 OTH AF: 0.943

Alfa AF: 0.931 Hom.: 54212

Bravo AF: 0.948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs10865972; hg19: chr3-52491447;