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3-52473778-G-A

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.Ser238=) 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

2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.13 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 499 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NISCHNM_007184.4 linkuse as main transcriptc.714G>A p.Ser238= synonymous_variant 7/21 ENST00000345716.9
NISCHNM_001276293.2 linkuse as main transcriptc.714G>A p.Ser238= synonymous_variant 7/13
NISCHNM_001276294.2 linkuse as main transcriptc.714G>A p.Ser238= synonymous_variant 7/14
NISCHXM_047447373.1 linkuse as main transcriptc.714G>A p.Ser238= synonymous_variant 7/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NISCHENST00000345716.9 linkuse as main transcriptc.714G>A p.Ser238= synonymous_variant 7/211 NM_007184.4 Q9Y2I1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00328
AC:
499
AN:
152198
Hom.:
1
Cov.:
32
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.:
11
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.:
31
Cov.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00328
AC:
499
AN:
152316
Hom.:
1
Cov.:
32
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.:
1
Bravo
AF:
0.00246
Asia WGS
AF:
0.000577
AC:
2
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 submitterclinical testingInvitaeMar 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.

Other links and lift over

dbSNP: rs76608301; hg19: chr3-52507794; COSMIC: COSV61900470; COSMIC: COSV61900470; API