Variant chr3-52473778-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_007184.4(NISCH):c.714G>A(p.Ser238Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,609,622 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 31 hom. )

Consequence

NISCH
NM_007184.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.13

Variant links:

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]

NISCH links:

NISCH (HGNC:):

NISCH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-52473778-G-A is Benign according to our data. Variant chr3-52473778-G-A is described in ClinVar as [Benign]. Clinvar id is 781969.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.13 with no splicing effect.

BS2

High AC in GnomAd4 at 499 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NISCH	NM_007184.4 linkuse as main transcript	c.714G>A	p.Ser238Ser	synonymous_variant	7/21	ENST00000345716.9	NP_009115.3	Q9Y2I1-1
NISCH	NM_001276293.2 linkuse as main transcript	c.714G>A	p.Ser238Ser	synonymous_variant	7/13		NP_001263222.2	Q9Y2I1
NISCH	NM_001276294.2 linkuse as main transcript	c.714G>A	p.Ser238Ser	synonymous_variant	7/14		NP_001263223.2	Q9Y2I1-4
NISCH	XM_047447373.1 linkuse as main transcript	c.714G>A	p.Ser238Ser	synonymous_variant	7/18		XP_047303329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NISCH	ENST00000345716.9 linkuse as main transcript	c.714G>A	p.Ser238Ser	synonymous_variant	7/21	1	NM_007184.4	ENSP00000339958.4		Q9Y2I1-1

Frequencies

GnomAD3 genomes

AF:

0.00328

AC:

499

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00497

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00442

AC:

1110

AN:

251120

Hom.:

AF XY:

0.00429

AC XY:

582

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.000579

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.00660

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00444

AC:

6469

AN:

1457306

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

3235

AN XY:

723956

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.000717

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00143

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.00488

Gnomad4 OTH exome

AF:

0.00374

GnomAD4 genome

AF:

0.00328

AC:

499

AN:

152316

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00497

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00418

Hom.:

Bravo

AF:

0.00246

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00328

EpiControl

AF:

0.00379

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.042

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over