rs10490625

Positions:

• chr2-118101980-G-A

Variant summary

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

The NM_016133.4(INSIG2):​c.245-1217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 152,240 control chromosomes in the GnomAD database, including 432 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 0.064 (432 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659

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=-0.51).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSIG2	NM_016133.4	c.245-1217G>A		intron_variant		ENST00000245787.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSIG2	ENST00000245787.9	c.245-1217G>A		intron_variant		1	NM_016133.4	P1

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9723 AN: 152122 Hom.: 428 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0883

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.0578

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

GnomAD4 genome AF: 0.0640 AC: 9746 AN: 152240 Hom.: 432 Cov.: 32 AF XY: 0.0674 AC XY: 5015 AN XY: 74432

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.0887

Gnomad4 ASJ AF: 0.0648

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.0632

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0697 Hom.: 99

Bravo AF: 0.0597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10490625; hg19: chr2-118859556; COSMIC: COSV55522200; COSMIC: COSV55522200;