12-53503200-G-A

Variant names:

• chr12-53503200-G-A
• rs2280448
• NM_134323.2:c.326+71G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134323.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARBP2	NM_134323.2	MANE Select	c.326+71G>A		intron	N/A	NP_599150.1
	TARBP2	NM_004178.5		c.263+71G>A		intron	N/A	NP_004169.3
	TARBP2	NM_134324.3		c.263+71G>A		intron	N/A	NP_599151.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARBP2	ENST00000266987.7	TSL:1 MANE Select	c.326+71G>A		intron	N/A	ENSP00000266987.2
	TARBP2	ENST00000456234.6	TSL:1	c.263+71G>A		intron	N/A	ENSP00000416077.2
	TARBP2	ENST00000549610.5	TSL:1	n.433+71G>A		intron	N/A

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

African (AFR) AF: 0.0717 AC: 2076 AN: 28934

American (AMR) AF: 0.0729 AC: 1930 AN: 26480

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 3188 AN: 20136

East Asian (EAS) AF: 0.0625 AC: 2078 AN: 33272

South Asian (SAS) AF: 0.0697 AC: 4650 AN: 66748

European-Finnish (FIN) AF: 0.108 AC: 4975 AN: 45858

Middle Eastern (MID) AF: 0.0870 AC: 401 AN: 4610

European-Non Finnish (NFE) AF: 0.158 AC: 163218 AN: 1035134

Other (OTH) AF: 0.130 AC: 7029 AN: 54116

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

African (AFR) AF: 0.0793 AC: 3295 AN: 41564

American (AMR) AF: 0.0846 AC: 1295 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3472

East Asian (EAS) AF: 0.0488 AC: 253 AN: 5186

South Asian (SAS) AF: 0.0638 AC: 308 AN: 4828

European-Finnish (FIN) AF: 0.109 AC: 1158 AN: 10608

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10678 AN: 68012

Other (OTH) AF: 0.103 AC: 219 AN: 2116

Alfa AF: 0.131 Hom.: 436

Bravo AF: 0.112

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.072
DANN	Benign	0.57
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2280448; hg19: chr12-53896984;