Variant 2-118103297-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_016133.4(INSIG2):c.345T>C(p.Phe115Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,613,400 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 30 hom. )

Consequence

INSIG2
NM_016133.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.28

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]

INSIG2 links:

INSIG2 (HGNC:):

INSIG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 2-118103297-T-C is Benign according to our data. Variant chr2-118103297-T-C is described in ClinVar as [Benign]. Clinvar id is 770694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00469 (6848/1461094) while in subpopulation MID AF= 0.0368 (212/5764). AF 95% confidence interval is 0.0327. There are 30 homozygotes in gnomad4_exome. There are 3467 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSIG2	NM_016133.4 linkuse as main transcript	c.345T>C	p.Phe115Phe	synonymous_variant	3/6	ENST00000245787.9	NP_057217.2	Q9Y5U4A0A024RAI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSIG2	ENST00000245787.9 linkuse as main transcript	c.345T>C	p.Phe115Phe	synonymous_variant	3/6	1	NM_016133.4	ENSP00000245787.4		Q9Y5U4

Frequencies

GnomAD3 genomes

AF:

0.00441

AC:

671

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00837

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00556

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00475

AC:

1193

AN:

251130

Hom.:

AF XY:

0.00498

AC XY:

676

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00538

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00386

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00586

Gnomad OTH exome

AF:

0.00817

GnomAD4 exome

AF:

0.00469

AC:

6848

AN:

1461094

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

3467

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00512

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00394

Gnomad4 FIN exome

AF:

0.00191

Gnomad4 NFE exome

AF:

0.00477

Gnomad4 OTH exome

AF:

0.00553

GnomAD4 genome

AF:

0.00440

AC:

670

AN:

152306

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

327

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00836

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00556

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00564

Hom.:

Bravo

AF:

0.00480

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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