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GeneBe

7-155302843-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_005542.6(INSIG1):c.801T>C(p.Ala267=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,584,232 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 56 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 61 hom. )

Consequence

INSIG1
NM_005542.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41
Variant links:
Genes affected
INSIG1 (HGNC:6083): (insulin induced gene 1) This gene encodes an endoplasmic reticulum membrane protein that regulates cholesterol metabolism, lipogenesis, and glucose homeostasis. The encoded protein has six transmembrane helices which contain an effector protein binding site. It binds the sterol-sensing domains of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and is essential for the sterol-mediated trafficking of these two proteins. It promotes the endoplasmic reticulum retention of SCAP and the ubiquitin-mediated degradation of HMG-CoA reductase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-155302843-T-C is Benign according to our data. Variant chr7-155302843-T-C is described in ClinVar as [Benign]. Clinvar id is 768219.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=-1.41 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
INSIG1NM_005542.6 linkuse as main transcriptc.801T>C p.Ala267= synonymous_variant 5/6 ENST00000340368.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
INSIG1ENST00000340368.9 linkuse as main transcriptc.801T>C p.Ala267= synonymous_variant 5/61 NM_005542.6 P1O15503-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0168
AC:
2559
AN:
152186
Hom.:
55
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0581
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00667
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000382
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00454
AC:
1142
AN:
251350
Hom.:
38
AF XY:
0.00319
AC XY:
433
AN XY:
135848
show subpopulations
Gnomad AFR exome
AF:
0.0612
Gnomad AMR exome
AF:
0.00284
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000290
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00181
AC:
2588
AN:
1431928
Hom.:
61
Cov.:
27
AF XY:
0.00154
AC XY:
1101
AN XY:
714422
show subpopulations
Gnomad4 AFR exome
AF:
0.0579
Gnomad4 AMR exome
AF:
0.00331
Gnomad4 ASJ exome
AF:
0.0000385
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000187
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000247
Gnomad4 OTH exome
AF:
0.00386
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0169
AC:
2572
AN:
152304
Hom.:
56
Cov.:
32
AF XY:
0.0166
AC XY:
1237
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0582
Gnomad4 AMR
AF:
0.00660
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000382
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.0109
Hom.:
16
Bravo
AF:
0.0194
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.000219
EpiControl
AF:
0.000415

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 testingInvitaeAug 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
2.9
Dann
Benign
0.66
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs61740679; hg19: chr7-155094553; API