12-53503200-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_134323.2(TARBP2):​c.326+71G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000076 in 1,315,604 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: TARBP2 NM_134323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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>C		intron	N/A	NP_599150.1
	TARBP2	NM_004178.5		c.263+71G>C		intron	N/A	NP_004169.3
	TARBP2	NM_134324.3		c.263+71G>C		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>C		intron	N/A	ENSP00000266987.2
	TARBP2	ENST00000456234.6	TSL:1	c.263+71G>C		intron	N/A	ENSP00000416077.2
	TARBP2	ENST00000549610.5	TSL:1	n.433+71G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.60e-7 AC: 1 AN: 1315604 Hom.: 0 Cov.: 30 AF XY: 0.00000156 AC XY: 1 AN XY: 641080

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28942

American (AMR) AF: 0.00 AC: 0 AN: 26490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20144

East Asian (EAS) AF: 0.00 AC: 0 AN: 33280

South Asian (SAS) AF: 0.00 AC: 0 AN: 66770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4614

European-Non Finnish (NFE) AF: 9.66e-7 AC: 1 AN: 1035362

Other (OTH) AF: 0.00 AC: 0 AN: 54124

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.043
DANN	Benign	0.61
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;