3-52484770-T-C

Variant names:

• chr3-52484770-T-C
• rs4687619
• NM_007184.4:c.1653+133T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007184.4(NISCH):​c.1653+133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 933,584 control chromosomes in the GnomAD database, including 426,173 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 (70421 hom., cov: 27)
  • Exomes 𝑓: 0.95 (355752 hom.)
• Consequence: NISCH NM_007184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.982 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.1653+133T>C		intron	N/A	NP_009115.3	Q9Y2I1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NISCH	ENST00000345716.9	TSL:1 MANE Select	c.1653+133T>C		intron	N/A	ENSP00000339958.4	Q9Y2I1-1
	NISCH	ENST00000479054.5	TSL:1	c.1653+133T>C		intron	N/A	ENSP00000418232.1	Q9Y2I1-1
	NISCH	ENST00000878266.1		c.1611+133T>C		intron	N/A	ENSP00000548325.1

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146072 AN: 151734 Hom.: 70361 Cov.: 27

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.957

GnomAD4 exome AF: 0.954 AC: 745617 AN: 781732 Hom.: 355752 AF XY: 0.954 AC XY: 383194 AN XY: 401482

African (AFR) AF: 0.990 AC: 19383 AN: 19580

American (AMR) AF: 0.960 AC: 29587 AN: 30818

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 16446 AN: 16940

East Asian (EAS) AF: 0.985 AC: 34805 AN: 35350

South Asian (SAS) AF: 0.980 AC: 58486 AN: 59662

European-Finnish (FIN) AF: 0.965 AC: 36754 AN: 38068

Middle Eastern (MID) AF: 0.964 AC: 4054 AN: 4206

European-Non Finnish (NFE) AF: 0.946 AC: 510829 AN: 540074

Other (OTH) AF: 0.952 AC: 35273 AN: 37034

GnomAD4 genome AF: 0.963 AC: 146191 AN: 151852 Hom.: 70421 Cov.: 27 AF XY: 0.965 AC XY: 71562 AN XY: 74184

African (AFR) AF: 0.990 AC: 40984 AN: 41404

American (AMR) AF: 0.946 AC: 14422 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3364 AN: 3468

East Asian (EAS) AF: 0.979 AC: 5031 AN: 5140

South Asian (SAS) AF: 0.980 AC: 4701 AN: 4798

European-Finnish (FIN) AF: 0.970 AC: 10205 AN: 10526

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64331 AN: 67956

Other (OTH) AF: 0.956 AC: 2022 AN: 2114

Alfa AF: 0.960 Hom.: 8717

Bravo AF: 0.962

Asia WGS AF: 0.966 AC: 3360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-0.84
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: rs4687619; hg19: chr3-52518786;