NM_016133.4:c.244+2538A>G

Variant names:

• chr2-118099338-A-G
• rs2161829
• NM_016133.4:c.244+2538A>G

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+2538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,000 control chromosomes in the GnomAD database, including 21,826 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 0.53 (21826 hom., cov: 33)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 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.244+2538A>G		intron	N/A	NP_057217.2
	INSIG2	NM_001321329.2		c.244+2538A>G		intron	N/A	NP_001308258.1
	INSIG2	NM_001321330.2		c.-80-3859A>G		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.244+2538A>G		intron	N/A	ENSP00000245787.4
	INSIG2	ENST00000411929.5	TSL:2	n.-114-3859A>G		intron	N/A	ENSP00000400126.1
	INSIG2	ENST00000467223.5	TSL:5	n.125+2912A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81015 AN: 151880 Hom.: 21810 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.533 AC: 81076 AN: 152000 Hom.: 21826 Cov.: 33 AF XY: 0.531 AC XY: 39446 AN XY: 74296

African (AFR) AF: 0.462 AC: 19148 AN: 41450

American (AMR) AF: 0.509 AC: 7777 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2010 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2674 AN: 5160

South Asian (SAS) AF: 0.545 AC: 2625 AN: 4818

European-Finnish (FIN) AF: 0.548 AC: 5779 AN: 10550

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39244 AN: 67964

Other (OTH) AF: 0.571 AC: 1208 AN: 2116

Alfa AF: 0.565 Hom.: 73121

Bravo AF: 0.528

Asia WGS AF: 0.540 AC: 1876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.57
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2161829; hg19: chr2-118856914;