dbSNP rs13003121: INSIG2:c.637-43G>A (chr2-118108238-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016133.4(INSIG2):c.637-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 1,355,860 control chromosomes in the GnomAD database, including 910 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 0.043 ( 201 hom., cov: 33)

Exomes 𝑓: 0.031 ( 709 hom. )

Consequence

INSIG2
NM_016133.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.350

Publications

4 publications found

Variant links:

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]

INSIG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.081 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INSIG2	NM_016133.4	MANE Select	c.637-43G>A	intron	N/A	NP_057217.2
INSIG2	NM_001321329.2		c.637-43G>A	intron	N/A	NP_001308258.1	Q9Y5U4
INSIG2	NM_001321330.2		c.313-43G>A	intron	N/A	NP_001308259.1	B4DQ23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INSIG2	ENST00000245787.9	TSL:1 MANE Select	c.637-43G>A	intron	N/A	ENSP00000245787.4	Q9Y5U4
INSIG2	ENST00000864770.1		c.637-43G>A	intron	N/A	ENSP00000534829.1
INSIG2	ENST00000864771.1		c.637-43G>A	intron	N/A	ENSP00000534830.1

Frequencies

GnomAD3 genomes

AF:

0.0432

AC:

6575

AN:

152114

Hom.:

202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0835

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0414

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.00547

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0305

Gnomad OTH

AF:

0.0493

GnomAD2 exomes

AF:

0.0256

AC:

5374

AN:

209930

AF XY:

0.0235

show subpopulations

Gnomad AFR exome

AF:

0.0807

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0558

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00595

Gnomad NFE exome

AF:

0.0284

Gnomad OTH exome

AF:

0.0312

GnomAD4 exome

AF:

0.0305

AC:

36744

AN:

1203628

Hom.:

709

Cov.:

AF XY:

0.0294

AC XY:

17912

AN XY:

609722

show subpopulations

African (AFR)

AF:

0.0865

AC:

2258

AN:

26108

American (AMR)

AF:

0.0254

AC:

844

AN:

33202

Ashkenazi Jewish (ASJ)

AF:

0.0605

AC:

1442

AN:

23822

East Asian (EAS)

AF:

0.0000553

AC:

AN:

36188

South Asian (SAS)

AF:

0.00855

AC:

625

AN:

73068

European-Finnish (FIN)

AF:

0.00707

AC:

374

AN:

52908

Middle Eastern (MID)

AF:

0.0404

AC:

206

AN:

5102

European-Non Finnish (NFE)

AF:

0.0324

AC:

29238

AN:

901890

Other (OTH)

AF:

0.0342

AC:

1755

AN:

51340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1583

3166

4749

6332

7915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1092

2184

3276

4368

5460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0432

AC:

6578

AN:

152232

Hom.:

201

Cov.:

AF XY:

0.0405

AC XY:

3015

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0833

AC:

3464

AN:

41566

American (AMR)

AF:

0.0413

AC:

631

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0594

AC:

206

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00725

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00547

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0305

AC:

2072

AN:

67986

Other (OTH)

AF:

0.0483

AC:

102

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

324

649

973

1298

1622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0385

Hom.:

Bravo

AF:

0.0492

Asia WGS

AF:

0.00693

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.7

(source)

DANN

Benign

0.67

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over