dbSNP rs3737813: TOR1AIP2:c.-147+4559T>G (chr1-179860877-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001199260.2(TOR1AIP2):c.-147+4559T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 985,348 control chromosomes in the GnomAD database, including 14,678 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 0.14 ( 1796 hom., cov: 32)

Exomes 𝑓: 0.17 ( 12882 hom. )

Consequence

TOR1AIP2
NM_001199260.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610

Publications

6 publications found

Variant links:

Genes affected

TOR1AIP2 (HGNC:24055): (torsin 1A interacting protein 2) One of the two protein isoforms encoded by this gene is a type II integral membrane protein found in the endoplasmic reticulum (ER). The encoded protein is a cofactor for the ATPase TorsinA, regulating the amount of TorsinA present in the ER compared to that found in the nuclear envelope. Defects in this protein are a cause of early onset primary dystonia, a neuromuscular disease. The other isoform encoded by this gene is an interferon alpha responsive protein whose cellular role has yet to be determined. [provided by RefSeq, Mar 2017]

TOR1AIP2 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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP2	NM_001199260.2 link	c.-147+4559T>G		intron_variant	Intron 3 of 6	ENST00000609928.6	NP_001186189.1	Q8NFQ8-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TOR1AIP2	ENST00000609928.6 link	c.-147+4559T>G	intron_variant	Intron 3 of 6	2	NM_001199260.2	ENSP00000477486.1	Q8NFQ8-1
TOR1AIP2	ENST00000367612.7 link	c.-146-8066T>G	intron_variant	Intron 2 of 5	1		ENSP00000356584.3	Q8NFQ8-1
TOR1AIP2	ENST00000482587.5 link	c.*3904T>G	3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000485355.1	Q9H496-1

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21256

AN:

152122

Hom.:

1794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0534

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.0876

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.128

GnomAD4 exome

AF:

0.174

AC:

144866

AN:

833108

Hom.:

12882

Cov.:

AF XY:

0.175

AC XY:

67196

AN XY:

384714

show subpopulations

African (AFR)

AF:

0.0414

AC:

653

AN:

15786

American (AMR)

AF:

0.128

AC:

126

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.0891

AC:

459

AN:

5152

East Asian (EAS)

AF:

0.125

AC:

455

AN:

3630

South Asian (SAS)

AF:

0.116

AC:

1911

AN:

16460

European-Finnish (FIN)

AF:

0.279

AC:

AN:

276

Middle Eastern (MID)

AF:

0.0901

AC:

146

AN:

1620

European-Non Finnish (NFE)

AF:

0.179

AC:

136682

AN:

761902

Other (OTH)

AF:

0.160

AC:

4357

AN:

27298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

7675

15350

23025

30700

38375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6540

13080

19620

26160

32700

<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:

0.140

AC:

21252

AN:

152240

Hom.:

1796

Cov.:

AF XY:

0.144

AC XY:

10704

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0534

AC:

2221

AN:

41560

American (AMR)

AF:

0.146

AC:

2232

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0876

AC:

304

AN:

3472

East Asian (EAS)

AF:

0.139

AC:

717

AN:

5174

South Asian (SAS)

AF:

0.119

AC:

572

AN:

4818

European-Finnish (FIN)

AF:

0.271

AC:

2871

AN:

10594

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11872

AN:

68000

Other (OTH)

AF:

0.125

AC:

265

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

906

1813

2719

3626

4532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<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:

0.152

Hom.:

3261

Bravo

AF:

0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.7

(source)

DANN

Benign

0.75

PhyloP100

-0.061

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over