chr3-52490558-C-A

Variant names:

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

Variant summary

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

The NM_007184.4(NISCH):​c.3614-147C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 1,124,192 control chromosomes in the GnomAD database, including 511,205 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 (70618 hom., cov: 33)
  • Exomes 𝑓: 0.95 (440587 hom.)
• Consequence: NISCH NM_007184.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 10 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=-0.87).
• 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.3614-147C>A		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>A		intron	N/A	ENSP00000339958.4	Q9Y2I1-1
	NISCH	ENST00000479054.5	TSL:1	c.3614-147C>A		intron	N/A	ENSP00000418232.1	Q9Y2I1-1
	NISCH	ENST00000878266.1		c.3572-147C>A		intron	N/A	ENSP00000548325.1

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146482 AN: 152160 Hom.: 70558 Cov.: 33

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.957

GnomAD4 exome AF: 0.952 AC: 925250 AN: 971914 Hom.: 440587 AF XY: 0.952 AC XY: 468792 AN XY: 492210

African (AFR) AF: 0.990 AC: 22688 AN: 22920

American (AMR) AF: 0.959 AC: 28482 AN: 29696

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 17372 AN: 17910

East Asian (EAS) AF: 0.984 AC: 36342 AN: 36924

South Asian (SAS) AF: 0.980 AC: 61064 AN: 62306

European-Finnish (FIN) AF: 0.966 AC: 37033 AN: 38332

Middle Eastern (MID) AF: 0.960 AC: 3007 AN: 3132

European-Non Finnish (NFE) AF: 0.945 AC: 677724 AN: 717046

Other (OTH) AF: 0.952 AC: 41538 AN: 43648

GnomAD4 genome AF: 0.963 AC: 146601 AN: 152278 Hom.: 70618 Cov.: 33 AF XY: 0.965 AC XY: 71806 AN XY: 74434

African (AFR) AF: 0.990 AC: 41141 AN: 41562

American (AMR) AF: 0.946 AC: 14476 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3368 AN: 3472

East Asian (EAS) AF: 0.979 AC: 5063 AN: 5172

South Asian (SAS) AF: 0.980 AC: 4730 AN: 4828

European-Finnish (FIN) AF: 0.969 AC: 10298 AN: 10624

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

European-Non Finnish (NFE) AF: 0.947 AC: 64371 AN: 68006

Other (OTH) AF: 0.957 AC: 2023 AN: 2114

Alfa AF: 0.960 Hom.: 12550

Bravo AF: 0.962

Asia WGS AF: 0.966 AC: 3357 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.52
DANN	Benign	0.60
PhyloP100		-0.17
Mutation Taster		=99/1	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: rs6810027; hg19: chr3-52524574;