rs13409050

Positions:

• chr2-118106194-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSIG2	NM_016133.4	c.370-543G>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.370-543G>A		intron_variant		1	NM_016133.4	ENSP00000245787	P1

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

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.0706

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0559

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0671

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0824 Hom.: 379

Bravo AF: 0.121

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.74

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: rs13409050; hg19: chr2-118863770;