rs10490625

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016133.4(INSIG2):​c.245-1217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 152,240 control chromosomes in the GnomAD database, including 432 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 0.064 ( 432 hom., cov: 32)

Consequence

INSIG2
NM_016133.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.659
Variant links:
Genes affected
INSIG2 (HGNC:20452): (insulin induced gene 2) The protein encoded by this gene is highly similar to the protein product encoded by gene INSIG1. Both INSIG1 protein and this protein are endoplasmic reticulum proteins that block the processing of sterol regulatory element binding proteins (SREBPs) by binding to SREBP cleavage-activating protein (SCAP), and thus prevent SCAP from escorting SREBPs to the Golgi. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
INSIG2NM_016133.4 linkuse as main transcriptc.245-1217G>A intron_variant ENST00000245787.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
INSIG2ENST00000245787.9 linkuse as main transcriptc.245-1217G>A intron_variant 1 NM_016133.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0639
AC:
9723
AN:
152122
Hom.:
428
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0227
Gnomad AMI
AF:
0.140
Gnomad AMR
AF:
0.0883
Gnomad ASJ
AF:
0.0648
Gnomad EAS
AF:
0.0200
Gnomad SAS
AF:
0.0631
Gnomad FIN
AF:
0.146
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.0734
Gnomad OTH
AF:
0.0578
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0640
AC:
9746
AN:
152240
Hom.:
432
Cov.:
32
AF XY:
0.0674
AC XY:
5015
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0227
Gnomad4 AMR
AF:
0.0887
Gnomad4 ASJ
AF:
0.0648
Gnomad4 EAS
AF:
0.0197
Gnomad4 SAS
AF:
0.0632
Gnomad4 FIN
AF:
0.146
Gnomad4 NFE
AF:
0.0734
Gnomad4 OTH
AF:
0.0639
Alfa
AF:
0.0697
Hom.:
99
Bravo
AF:
0.0597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
15
DANN
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs10490625; hg19: chr2-118859556; COSMIC: COSV55522200; COSMIC: COSV55522200; API