chr2-118106298-C-T

Position:

• chr2-118106298-C-T

Variant summary

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

The NM_016133.4(INSIG2):​c.370-439C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,236 control chromosomes in the GnomAD database, including 51,280 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 0.82 (51280 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432

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=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSIG2	NM_016133.4	c.370-439C>T		intron_variant		ENST00000245787.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSIG2	ENST00000245787.9	c.370-439C>T		intron_variant		1	NM_016133.4	P1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124412 AN: 152118 Hom.: 51237 Cov.: 32

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.818 AC: 124514 AN: 152236 Hom.: 51280 Cov.: 32 AF XY: 0.815 AC XY: 60631 AN XY: 74422

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.829

Alfa AF: 0.835 Hom.: 88629

Bravo AF: 0.813

Asia WGS AF: 0.636 AC: 2215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.63

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: rs9308762; hg19: chr2-118863874;