chr2-118092274-A-G

Position:

• chr2-118092274-A-G

Variant summary

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

The NM_016133.4(INSIG2):​c.-139+3733A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0624 in 152,276 control chromosomes in the GnomAD database, including 421 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 0.062 (421 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSIG2	NM_016133.4	c.-139+3733A>G		intron_variant		ENST00000245787.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSIG2	ENST00000245787.9	c.-139+3733A>G		intron_variant		1	NM_016133.4	P1

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9507 AN: 152158 Hom.: 422 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0624 AC: 9499 AN: 152276 Hom.: 421 Cov.: 32 AF XY: 0.0601 AC XY: 4477 AN XY: 74454

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.0446

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0543

Gnomad4 FIN AF: 0.0642

Gnomad4 NFE AF: 0.0998

Gnomad4 OTH AF: 0.0607

Alfa AF: 0.0867 Hom.: 78

Bravo AF: 0.0593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.43

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: rs12464355; hg19: chr2-118849850;