NM_016133.4:c.370-439C>T

Variant names:

• chr2-118106298-C-T
• rs9308762
• NM_016133.4:c.370-439C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016133.4(INSIG2):​c.370-439C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,236 control chromosomes in the GnomAD database, including 51,280 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 0.82 (51280 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432
• Publications: 17 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSIG2	NM_016133.4	c.370-439C>T		intron_variant	Intron 3 of 5	ENST00000245787.9	NP_057217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INSIG2	ENST00000245787.9	c.370-439C>T		intron_variant	Intron 3 of 5	1	NM_016133.4	ENSP00000245787.4

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124412 AN: 152118 Hom.: 51237 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.830

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.818 AC: 124514 AN: 152236 Hom.: 51280 Cov.: 32 AF XY: 0.815 AC XY: 60631 AN XY: 74422

African (AFR) AF: 0.848 AC: 35238 AN: 41542

American (AMR) AF: 0.756 AC: 11560 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2926 AN: 3472

East Asian (EAS) AF: 0.495 AC: 2561 AN: 5172

South Asian (SAS) AF: 0.722 AC: 3483 AN: 4826

European-Finnish (FIN) AF: 0.818 AC: 8674 AN: 10602

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57322 AN: 68010

Other (OTH) AF: 0.829 AC: 1752 AN: 2114

Alfa AF: 0.828 Hom.: 208009

Bravo AF: 0.813

Asia WGS AF: 0.636 AC: 2215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9308762; hg19: chr2-118863874;