chr12-53503200-G-A

Position:

• chr12-53503200-G-A

Variant summary

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

The NM_134323.2(TARBP2):​c.326+71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,467,580 control chromosomes in the GnomAD database, including 15,672 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 0.12 (1183 hom., cov: 33)
  • Exomes 𝑓: 0.14 (14489 hom.)
• Consequence: TARBP2 NM_134323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

TARBP2 (HGNC:11569): (TARBP2 subunit of RISC loading complex) HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene binds between the bulge and the loop of the HIV-1 TAR RNA regulatory element and activates HIV-1 gene expression in synergy with the viral Tat protein. Alternative splicing results in multiple transcript variants encoding different isoforms. This gene also has a pseudogene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TARBP2	NM_134323.2	c.326+71G>A		intron_variant		ENST00000266987.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TARBP2	ENST00000266987.7	c.326+71G>A		intron_variant		1	NM_134323.2	P4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17821 AN: 152174 Hom.: 1183 Cov.: 33

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0487

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.144 AC: 189545 AN: 1315288 Hom.: 14489 Cov.: 30 AF XY: 0.142 AC XY: 91127 AN XY: 640904

Gnomad4 AFR exome AF: 0.0717

Gnomad4 AMR exome AF: 0.0729

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.0697

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.117 AC: 17819 AN: 152292 Hom.: 1183 Cov.: 33 AF XY: 0.113 AC XY: 8431 AN XY: 74464

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0488

Gnomad4 SAS AF: 0.0638

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.103

Alfa AF: 0.136 Hom.: 202

Bravo AF: 0.112

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.072
DANN	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs2280448; hg19: chr12-53896984;