3-52472410-C-T

Variant names:

• chr3-52472410-C-T
• rs6784615
• NM_007184.4:c.669+12C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 87 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.972 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.669+12C>T		intron	N/A	NP_009115.3	Q9Y2I1-1
	NISCH	NM_001276293.2		c.669+12C>T		intron	N/A	NP_001263222.2	C9J715
	NISCH	NM_001276294.2		c.669+12C>T		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.669+12C>T		intron	N/A	ENSP00000339958.4	Q9Y2I1-1
	NISCH	ENST00000479054.5	TSL:1	c.669+12C>T		intron	N/A	ENSP00000418232.1	Q9Y2I1-1
	NISCH	ENST00000488380.5	TSL:1	c.669+12C>T		intron	N/A	ENSP00000417812.1	C9J715

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

GnomAD2 exomes AF: 0.955 AC: 240087 AN: 251354 AF XY: 0.954

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 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

African (AFR) AF: 0.980 AC: 32687 AN: 33370

American (AMR) AF: 0.959 AC: 42886 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 25290 AN: 26114

East Asian (EAS) AF: 0.982 AC: 38989 AN: 39692

South Asian (SAS) AF: 0.956 AC: 82362 AN: 86172

European-Finnish (FIN) AF: 0.965 AC: 51458 AN: 53340

Middle Eastern (MID) AF: 0.955 AC: 5465 AN: 5722

European-Non Finnish (NFE) AF: 0.941 AC: 1042385 AN: 1108306

Other (OTH) AF: 0.945 AC: 56929 AN: 60242

GnomAD4 genome AF: 0.957 AC: 145767 AN: 152340 Hom.: 69780 Cov.: 34 AF XY: 0.959 AC XY: 71442 AN XY: 74496

African (AFR) AF: 0.980 AC: 40765 AN: 41582

American (AMR) AF: 0.945 AC: 14461 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3361 AN: 3472

East Asian (EAS) AF: 0.976 AC: 5059 AN: 5182

South Asian (SAS) AF: 0.956 AC: 4618 AN: 4830

European-Finnish (FIN) AF: 0.968 AC: 10279 AN: 10622

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64080 AN: 68030

Other (OTH) AF: 0.955 AC: 2015 AN: 2110

Alfa AF: 0.946 Hom.: 225994

Bravo AF: 0.957

Asia WGS AF: 0.954 AC: 3317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.90
DANN	Benign	0.59
PhyloP100		-0.082
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs6784615; hg19: chr3-52506426; COSMIC: COSV61898546; COSMIC: COSV61898546;