NM_016133.4:c.245-1217G>A

Variant names:

• chr2-118101980-G-A
• rs10490625
• NM_016133.4:c.245-1217G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.51).
• 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 rank	MANE	Protein	UniProt
INSIG2	NM_016133.4	c.245-1217G>A		intron_variant	Intron 2 of 5	ENST00000245787.9	NP_057217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INSIG2	ENST00000245787.9	c.245-1217G>A		intron_variant	Intron 2 of 5	1	NM_016133.4	ENSP00000245787.4

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

African (AFR) AF: 0.0227 AC: 944 AN: 41538

American (AMR) AF: 0.0887 AC: 1357 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3472

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5186

South Asian (SAS) AF: 0.0632 AC: 305 AN: 4826

European-Finnish (FIN) AF: 0.146 AC: 1552 AN: 10600

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0734 AC: 4991 AN: 68006

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0664 Hom.: 150

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
PhyloP100		0.66
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: rs10490625; hg19: chr2-118859556; COSMIC: COSV55522200; COSMIC: COSV55522200;