rs11889497

chr2-118104888-T-G

Variant summary

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

The NM_016133.4(INSIG2):c.369+1567T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,208 control chromosomes in the GnomAD database, including 1,566 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 0.11 (1566 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSIG2	NM_016133.4	c.369+1567T>G		intron_variant		ENST00000245787.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSIG2	ENST00000245787.9	c.369+1567T>G		intron_variant		1	NM_016133.4	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17255 AN: 152090 Hom.: 1559 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0514

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.114 AC: 17283 AN: 152208 Hom.: 1566 Cov.: 32 AF XY: 0.112 AC XY: 8323 AN XY: 74424

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.0708

Gnomad4 ASJ AF: 0.0853

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0573

Gnomad4 FIN AF: 0.0514

Gnomad4 NFE AF: 0.0681

Gnomad4 OTH AF: 0.107

Alfa AF: 0.101 Hom.: 145

Bravo AF: 0.120

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.0
Dann	Benign	0.46

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: rs11889497; hg19: chr2-118862464;