chr2-118102895-C-T

Variant names:

• chr2-118102895-C-T
• rs889904
• NM_016133.4:c.245-302C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016133.4(INSIG2):​c.245-302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,986 control chromosomes in the GnomAD database, including 19,821 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 0.50 (19821 hom., cov: 32)
• Consequence: INSIG2 NM_016133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 8 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSIG2	NM_016133.4	c.245-302C>T		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.245-302C>T		intron_variant	Intron 2 of 5	1	NM_016133.4	ENSP00000245787.4

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76248 AN: 151868 Hom.: 19796 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.502 AC: 76323 AN: 151986 Hom.: 19821 Cov.: 32 AF XY: 0.499 AC XY: 37067 AN XY: 74290

African (AFR) AF: 0.611 AC: 25305 AN: 41442

American (AMR) AF: 0.429 AC: 6558 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1597 AN: 3466

East Asian (EAS) AF: 0.127 AC: 658 AN: 5162

South Asian (SAS) AF: 0.400 AC: 1929 AN: 4828

European-Finnish (FIN) AF: 0.483 AC: 5087 AN: 10534

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33603 AN: 67966

Other (OTH) AF: 0.490 AC: 1035 AN: 2112

Alfa AF: 0.491 Hom.: 47457

Bravo AF: 0.501

Asia WGS AF: 0.314 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.72
PhyloP100		-2.1
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: rs889904; hg19: chr2-118860471;