rs13003121

Positions:

• chr2-118108238-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016133.4(INSIG2):​c.637-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 1,355,860 control chromosomes in the GnomAD database, including 910 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 0.043 (201 hom., cov: 33)
  • Exomes 𝑓: 0.031 (709 hom.)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.081 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSIG2	NM_016133.4	c.637-43G>A		intron_variant		ENST00000245787.9	NP_057217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSIG2	ENST00000245787.9	c.637-43G>A		intron_variant		1	NM_016133.4	ENSP00000245787.4

Frequencies

GnomAD3 genomes AF: 0.0432 AC: 6575 AN: 152114 Hom.: 202 Cov.: 33

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.00547

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0305

Gnomad OTH AF: 0.0493

GnomAD3 exomes AF: 0.0256 AC: 5374 AN: 209930 Hom.: 101 AF XY: 0.0235 AC XY: 2696 AN XY: 114602

Gnomad AFR exome AF: 0.0807

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0558

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00714

Gnomad FIN exome AF: 0.00595

Gnomad NFE exome AF: 0.0284

Gnomad OTH exome AF: 0.0312

GnomAD4 exome AF: 0.0305 AC: 36744 AN: 1203628 Hom.: 709 Cov.: 17 AF XY: 0.0294 AC XY: 17912 AN XY: 609722

Gnomad4 AFR exome AF: 0.0865

Gnomad4 AMR exome AF: 0.0254

Gnomad4 ASJ exome AF: 0.0605

Gnomad4 EAS exome AF: 0.0000553

Gnomad4 SAS exome AF: 0.00855

Gnomad4 FIN exome AF: 0.00707

Gnomad4 NFE exome AF: 0.0324

Gnomad4 OTH exome AF: 0.0342

GnomAD4 genome AF: 0.0432 AC: 6578 AN: 152232 Hom.: 201 Cov.: 33 AF XY: 0.0405 AC XY: 3015 AN XY: 74434

Gnomad4 AFR AF: 0.0833

Gnomad4 AMR AF: 0.0413

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.00547

Gnomad4 NFE AF: 0.0305

Gnomad4 OTH AF: 0.0483

Alfa AF: 0.0375 Hom.: 25

Bravo AF: 0.0492

Asia WGS AF: 0.00693 AC: 24 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs13003121; hg19: chr2-118865814;