rs6784615

chr3-52472410-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NISCH	NM_007184.4	c.669+12C>T		intron_variant		ENST00000345716.9
NISCH	NM_001276293.2	c.669+12C>T		intron_variant
NISCH	NM_001276294.2	c.669+12C>T		intron_variant
NISCH	XM_047447373.1	c.669+12C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NISCH	ENST00000345716.9	c.669+12C>T		intron_variant		1	NM_007184.4

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145652 AN: 152222 Hom.: 69724 Cov.: 34

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

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.: 32 AF XY: 0.946 AC XY: 685943 AN XY: 725462

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.: 34 AF XY: 0.959 AC XY: 71442 AN XY: 74496

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

Other links and lift over

dbSNP: rs6784615; hg19: chr3-52506426; COSMIC: COSV61898546; COSMIC: COSV61898546;