rs17047757

Variant names:

• chr2-118103859-A-G
• rs17047757
• NM_016133.4:c.369+538A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_016133.4(INSIG2):​c.369+538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 152,192 control chromosomes in the GnomAD database, including 756 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 0.084 (756 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 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+538A>G		intron	N/A	NP_057217.2
	INSIG2	NM_001321329.2		c.369+538A>G		intron	N/A	NP_001308258.1
	INSIG2	NM_001321330.2		c.45+538A>G		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+538A>G		intron	N/A	ENSP00000245787.4
	INSIG2	ENST00000411929.5	TSL:2	n.11+538A>G		intron	N/A	ENSP00000400126.1
	INSIG2	ENST00000467223.5	TSL:5	n.250+538A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12764 AN: 152074 Hom.: 755 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.0984

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.0896

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

GnomAD4 genome AF: 0.0839 AC: 12772 AN: 152192 Hom.: 756 Cov.: 32 AF XY: 0.0842 AC XY: 6262 AN XY: 74392

African (AFR) AF: 0.0243 AC: 1009 AN: 41546

American (AMR) AF: 0.163 AC: 2486 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1290 AN: 5160

South Asian (SAS) AF: 0.0985 AC: 475 AN: 4822

European-Finnish (FIN) AF: 0.0808 AC: 856 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0879 AC: 5974 AN: 68002

Other (OTH) AF: 0.0887 AC: 187 AN: 2108

Alfa AF: 0.0867 Hom.: 803

Bravo AF: 0.0911

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.33		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17047757; hg19: chr2-118861435;