2-118091437-G-C

Position:

• chr2-118091437-G-C

Variant summary

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

The NM_016133.4(INSIG2):​c.-139+2896G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,134 control chromosomes in the GnomAD database, including 4,743 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 0.25 (4743 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSIG2	NM_016133.4	c.-139+2896G>C		intron_variant		ENST00000245787.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSIG2	ENST00000245787.9	c.-139+2896G>C		intron_variant		1	NM_016133.4	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37374 AN: 152016 Hom.: 4739 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.246 AC: 37399 AN: 152134 Hom.: 4743 Cov.: 32 AF XY: 0.244 AC XY: 18158 AN XY: 74380

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.234

Alfa AF: 0.142 Hom.: 273

Bravo AF: 0.243

Asia WGS AF: 0.197 AC: 688 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.47

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: rs13393332; hg19: chr2-118849013;