Variant rs6784615 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007184.4(NISCH):c.669+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.947 in 1,610,018 control chromosomes in the GnomAD database, including 721,765 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 ( 69780 hom., cov: 34)

Exomes 𝑓: 0.95 ( 651985 hom. )

Consequence

NISCH
NM_007184.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0820

Variant links:

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]

NISCH links:

NISCH (HGNC:):

NISCH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
NISCH	NM_007184.4 linkuse as main transcript	c.669+12C>T	intron_variant	ENST00000345716.9	NP_009115.3	Q9Y2I1-1
NISCH	NM_001276293.2 linkuse as main transcript	c.669+12C>T	intron_variant		NP_001263222.2	Q9Y2I1
NISCH	NM_001276294.2 linkuse as main transcript	c.669+12C>T	intron_variant		NP_001263223.2	Q9Y2I1-4
NISCH	XM_047447373.1 linkuse as main transcript	c.669+12C>T	intron_variant		XP_047303329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NISCH	ENST00000345716.9 linkuse as main transcript	c.669+12C>T		intron_variant		1	NM_007184.4	ENSP00000339958.4		Q9Y2I1-1

Frequencies

GnomAD3 genomes

AF:

0.957

AC:

145652

AN:

152222

Hom.:

69724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.980

Gnomad AMI

AF:

0.931

Gnomad AMR

AF:

0.945

Gnomad ASJ

AF:

0.968

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.956

Gnomad FIN

AF:

0.968

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.942

Gnomad OTH

AF:

0.955

GnomAD3 exomes

AF:

0.955

AC:

240087

AN:

251354

Hom.:

114714

AF XY:

0.954

AC XY:

129578

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.981

Gnomad AMR exome

AF:

0.961

Gnomad ASJ exome

AF:

0.970

Gnomad EAS exome

AF:

0.981

Gnomad SAS exome

AF:

0.956

Gnomad FIN exome

AF:

0.966

Gnomad NFE exome

AF:

0.942

Gnomad OTH exome

AF:

0.946

GnomAD4 exome

AF:

0.946

AC:

1378451

AN:

1457678

Hom.:

651985

Cov.:

AF XY:

0.946

AC XY:

685943

AN XY:

725462

show subpopulations

Gnomad4 AFR exome

AF:

0.980

Gnomad4 AMR exome

AF:

0.959

Gnomad4 ASJ exome

AF:

0.968

Gnomad4 EAS exome

AF:

0.982

Gnomad4 SAS exome

AF:

0.956

Gnomad4 FIN exome

AF:

0.965

Gnomad4 NFE exome

AF:

0.941

Gnomad4 OTH exome

AF:

0.945

GnomAD4 genome

AF:

0.957

AC:

145767

AN:

152340

Hom.:

69780

Cov.:

AF XY:

0.959

AC XY:

71442

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.980

Gnomad4 AMR

AF:

0.945

Gnomad4 ASJ

AF:

0.968

Gnomad4 EAS

AF:

0.976

Gnomad4 SAS

AF:

0.956

Gnomad4 FIN

AF:

0.968

Gnomad4 NFE

AF:

0.942

Gnomad4 OTH

AF:

0.955

Alfa

AF:

0.945

Hom.:

92283

Bravo

AF:

0.957

Asia WGS

AF:

0.954

AC:

3317

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.90

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over