rs113515

Positions:

• chr22-43160916-C-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TSPO	NM_000714.6	c.183-136C>G		intron_variant		ENST00000337554.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPO	ENST00000337554.8	c.183-136C>G		intron_variant		1	NM_000714.6	P1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60283 AN: 152030 Hom.: 12559 Cov.: 33

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

Gnomad4 AFR exome AF: 0.459

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.396

Gnomad4 EAS exome AF: 0.000855

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.395

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.397 AC: 60345 AN: 152148 Hom.: 12574 Cov.: 33 AF XY: 0.390 AC XY: 29027 AN XY: 74380

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.00675

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.415

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	17
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs113515; hg19: chr22-43556922;