chr2-118106194-G-A

Variant names:

• chr2-118106194-G-A
• rs13409050
• NM_016133.4:c.370-543G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016133.4(INSIG2):​c.370-543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,182 control chromosomes in the GnomAD database, including 1,572 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 0.11 (1572 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.985
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSIG2	NM_016133.4	MANE Select	c.370-543G>A		intron	N/A	NP_057217.2
	INSIG2	NM_001321329.2		c.370-543G>A		intron	N/A	NP_001308258.1	Q9Y5U4
	INSIG2	NM_001321330.2		c.46-543G>A		intron	N/A	NP_001308259.1	B4DQ23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSIG2	ENST00000245787.9	TSL:1 MANE Select	c.370-543G>A		intron	N/A	ENSP00000245787.4	Q9Y5U4
	INSIG2	ENST00000864770.1		c.370-543G>A		intron	N/A	ENSP00000534829.1
	INSIG2	ENST00000864771.1		c.370-543G>A		intron	N/A	ENSP00000534830.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17277 AN: 152064 Hom.: 1569 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.0707

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.114 AC: 17295 AN: 152182 Hom.: 1572 Cov.: 32 AF XY: 0.112 AC XY: 8331 AN XY: 74408

African (AFR) AF: 0.247 AC: 10244 AN: 41490

American (AMR) AF: 0.0706 AC: 1079 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3470

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.0559 AC: 270 AN: 4830

European-Finnish (FIN) AF: 0.0515 AC: 546 AN: 10602

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4561 AN: 68004

Other (OTH) AF: 0.106 AC: 225 AN: 2116

Alfa AF: 0.0844 Hom.: 462

Bravo AF: 0.121

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.74
PhyloP100		0.98
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: rs13409050; hg19: chr2-118863770;