2-118091437-G-C

Variant names:

• chr2-118091437-G-C
• rs13393332
• NM_016133.4:c.-139+2896G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016133.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSIG2	NM_016133.4	MANE Select	c.-139+2896G>C		intron	N/A	NP_057217.2
	INSIG2	NM_001321329.2		c.-139+2771G>C		intron	N/A	NP_001308258.1
	INSIG2	NM_001321330.2		c.-81+2896G>C		intron	N/A	NP_001308259.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSIG2	ENST00000245787.9	TSL:1 MANE Select	c.-139+2896G>C		intron	N/A	ENSP00000245787.4
	INSIG2	ENST00000411929.5	TSL:2	n.-115+2896G>C		intron	N/A	ENSP00000400126.1
	INSIG2	ENST00000467223.5	TSL:5	n.117+2771G>C		intron	N/A

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

African (AFR) AF: 0.275 AC: 11412 AN: 41472

American (AMR) AF: 0.189 AC: 2894 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3468

East Asian (EAS) AF: 0.114 AC: 590 AN: 5190

South Asian (SAS) AF: 0.254 AC: 1224 AN: 4820

European-Finnish (FIN) AF: 0.185 AC: 1964 AN: 10598

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17642 AN: 67988

Other (OTH) AF: 0.234 AC: 495 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.47
PhyloP100		0.051
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: rs13393332; hg19: chr2-118849013;