rs10490624

chr2-118104916-T-C

Variant summary

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

The NM_016133.4(INSIG2):c.369+1595T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,310 control chromosomes in the GnomAD database, including 890 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 0.10 (890 hom., cov: 33)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.902

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSIG2	NM_016133.4	c.369+1595T>C		intron_variant		ENST00000245787.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSIG2	ENST00000245787.9	c.369+1595T>C		intron_variant		1	NM_016133.4	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15966 AN: 152192 Hom.: 888 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0217

Gnomad SAS AF: 0.0705

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0969

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.105 AC: 15992 AN: 152310 Hom.: 890 Cov.: 33 AF XY: 0.105 AC XY: 7850 AN XY: 74482

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.0706

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0969

Gnomad4 OTH AF: 0.112

Alfa AF: 0.100 Hom.: 740

Bravo AF: 0.108

Asia WGS AF: 0.0650 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	9.2
Dann	Benign	0.75

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: rs10490624; hg19: chr2-118862492; COSMIC: COSV55522209; COSMIC: COSV55522209;