Genetic Variant NM_000714.6:c.183-136C>G (chr22-43160916-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000714.6(TSPO):c.183-136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,066,112 control chromosomes in the GnomAD database, including 80,307 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 0.40 ( 12574 hom., cov: 33)

Exomes 𝑓: 0.37 ( 67733 hom. )

Consequence

TSPO
NM_000714.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.865

Publications

10 publications found

Variant links:

Genes affected

TSPO (HGNC:1158): (translocator protein) Present mainly in the mitochondrial compartment of peripheral tissues, the protein encoded by this gene interacts with some benzodiazepines and has different affinities than its endogenous counterpart. The protein is a key factor in the flow of cholesterol into mitochondria to permit the initiation of steroid hormone synthesis. Alternatively spliced transcript variants have been reported; one of the variants lacks an internal exon and is considered non-coding, and the other variants encode the same protein. [provided by RefSeq, Feb 2012]

TSPO links:

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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=-0.5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPO	NM_000714.6 link	c.183-136C>G		intron_variant	Intron 2 of 3	ENST00000337554.8	NP_000705.2	P30536-1O76068

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPO	ENST00000337554.8 link	c.183-136C>G		intron_variant	Intron 2 of 3	1	NM_000714.6	ENSP00000338004.3		P30536-1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60283

AN:

152030

Hom.:

12559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.447

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.417

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.00654

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.421

GnomAD4 exome

AF:

0.374

AC:

341720

AN:

913964

Hom.:

67733

AF XY:

0.371

AC XY:

169254

AN XY:

455710

show subpopulations

African (AFR)

AF:

0.459

AC:

9620

AN:

20962

American (AMR)

AF:

0.399

AC:

7073

AN:

17734

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

6307

AN:

15924

East Asian (EAS)

AF:

0.000855

AC:

AN:

32746

South Asian (SAS)

AF:

0.285

AC:

14740

AN:

51702

European-Finnish (FIN)

AF:

0.361

AC:

14589

AN:

40464

Middle Eastern (MID)

AF:

0.447

AC:

1336

AN:

2990

European-Non Finnish (NFE)

AF:

0.395

AC:

273110

AN:

691040

Other (OTH)

AF:

0.369

AC:

14917

AN:

40402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

10074

20148

30223

40297

50371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7598

15196

22794

30392

37990

<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:

0.397

AC:

60345

AN:

152148

Hom.:

12574

Cov.:

AF XY:

0.390

AC XY:

29027

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.447

AC:

18548

AN:

41492

American (AMR)

AF:

0.418

AC:

6389

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1384

AN:

3466

East Asian (EAS)

AF:

0.00675

AC:

AN:

5184

South Asian (SAS)

AF:

0.264

AC:

1271

AN:

4822

European-Finnish (FIN)

AF:

0.346

AC:

3663

AN:

10594

Middle Eastern (MID)

AF:

0.493

AC:

144

AN:

292

European-Non Finnish (NFE)

AF:

0.407

AC:

27687

AN:

67994

Other (OTH)

AF:

0.415

AC:

876

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1825

3651

5476

7302

9127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.419

Hom.:

1681

Bravo

AF:

0.403

Asia WGS

AF:

0.160

AC:

559

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

0.86

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over