chr3-52490558-C-T

Variant names:

• chr3-52490558-C-T
• rs6810027
• NM_007184.4:c.3614-147C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007184.4(NISCH):​c.3614-147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,294 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NISCH NM_007184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.3614-147C>T		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.3614-147C>T		intron	N/A	ENSP00000339958.4	Q9Y2I1-1
	NISCH	ENST00000479054.5	TSL:1	c.3614-147C>T		intron	N/A	ENSP00000418232.1	Q9Y2I1-1
	NISCH	ENST00000878266.1		c.3572-147C>T		intron	N/A	ENSP00000548325.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000103 AC: 1 AN: 972392 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 492438

African (AFR) AF: 0.0000436 AC: 1 AN: 22922

American (AMR) AF: 0.00 AC: 0 AN: 29710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17914

East Asian (EAS) AF: 0.00 AC: 0 AN: 36928

South Asian (SAS) AF: 0.00 AC: 0 AN: 62314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 717474

Other (OTH) AF: 0.00 AC: 0 AN: 43654

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152294 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74448

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.89
PhyloP100		-0.17

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: rs6810027; hg19: chr3-52524574;