rs17528324

Variant names:

• chr2-118098580-G-A
• rs17528324
• NM_016133.4:c.244+1780G>A

Variant summary

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

The NM_016133.4(INSIG2):​c.244+1780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 152,264 control chromosomes in the GnomAD database, including 373 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 0.054 (373 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSIG2	NM_016133.4	c.244+1780G>A		intron_variant	Intron 2 of 5	ENST00000245787.9	NP_057217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INSIG2	ENST00000245787.9	c.244+1780G>A		intron_variant	Intron 2 of 5	1	NM_016133.4	ENSP00000245787.4

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 8264 AN: 152146 Hom.: 372 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0422

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.0439

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

GnomAD4 genome AF: 0.0543 AC: 8273 AN: 152264 Hom.: 373 Cov.: 32 AF XY: 0.0598 AC XY: 4452 AN XY: 74436

African (AFR) AF: 0.0114 AC: 476 AN: 41578

American (AMR) AF: 0.0946 AC: 1446 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 158 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5174

South Asian (SAS) AF: 0.0425 AC: 205 AN: 4828

European-Finnish (FIN) AF: 0.162 AC: 1717 AN: 10592

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0594 AC: 4037 AN: 68012

Other (OTH) AF: 0.0435 AC: 92 AN: 2116

Alfa AF: 0.0576 Hom.: 192

Bravo AF: 0.0479

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.78
PhyloP100		0.017
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: rs17528324; hg19: chr2-118856156; COSMIC: COSV55522193; COSMIC: COSV55522193;