chr2-118104916-T-C

Variant names:

• chr2-118104916-T-C
• rs10490624
• NM_016133.4:c.369+1595T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016133.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSIG2	NM_016133.4	MANE Select	c.369+1595T>C		intron	N/A	NP_057217.2
	INSIG2	NM_001321329.2		c.369+1595T>C		intron	N/A	NP_001308258.1
	INSIG2	NM_001321330.2		c.45+1595T>C		intron	N/A	NP_001308259.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSIG2	ENST00000245787.9	TSL:1 MANE Select	c.369+1595T>C		intron	N/A	ENSP00000245787.4
	INSIG2	ENST00000411929.5	TSL:2	n.11+1595T>C		intron	N/A	ENSP00000400126.1
	INSIG2	ENST00000467223.5	TSL:5	n.250+1595T>C		intron	N/A

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

African (AFR) AF: 0.111 AC: 4630 AN: 41556

American (AMR) AF: 0.129 AC: 1978 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3472

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5192

South Asian (SAS) AF: 0.0706 AC: 341 AN: 4832

European-Finnish (FIN) AF: 0.144 AC: 1524 AN: 10608

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0969 AC: 6595 AN: 68028

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.0980 Hom.: 1847

Bravo AF: 0.108

Asia WGS AF: 0.0650 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.2
DANN	Benign	0.75
PhyloP100		0.90
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: rs10490624; hg19: chr2-118862492; COSMIC: COSV55522209; COSMIC: COSV55522209;