chr12-53505849-T-C

Variant names:

• chr12-53505849-T-C
• rs61499963
• NM_134323.2:c.942T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_134323.2(TARBP2):​c.942T>C​(p.Ile314Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,613,288 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (52 hom.)
• Consequence: TARBP2 NM_134323.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.001648
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0760
• Publications: 4 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 12-53505849-T-C is Benign according to our data. Variant chr12-53505849-T-C is described in ClinVar as Benign. ClinVar VariationId is 776709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.076 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0565 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARBP2	NM_134323.2	MANE Select	c.942T>C	p.Ile314Ile	splice_region synonymous	Exon 8 of 9	NP_599150.1	Q15633-1
	TARBP2	NM_004178.5		c.879T>C	p.Ile293Ile	splice_region synonymous	Exon 8 of 9	NP_004169.3
	TARBP2	NM_134324.3		c.879T>C	p.Ile293Ile	splice_region synonymous	Exon 8 of 9	NP_599151.2	Q15633-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARBP2	ENST00000266987.7	TSL:1 MANE Select	c.942T>C	p.Ile314Ile	splice_region synonymous	Exon 8 of 9	ENSP00000266987.2	Q15633-1
	TARBP2	ENST00000456234.6	TSL:1	c.879T>C	p.Ile293Ile	splice_region synonymous	Exon 8 of 9	ENSP00000416077.2	Q15633-2
	TARBP2	ENST00000550147.5	TSL:1	n.*583T>C		splice_region non_coding_transcript_exon	Exon 8 of 9	ENSP00000450320.1	F8VP94

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2524 AN: 151868 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00433

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.00431 AC: 1079 AN: 250600 AF XY: 0.00311

Gnomad AFR exome AF: 0.0603

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00158 AC: 2302 AN: 1461302 Hom.: 52 Cov.: 32 AF XY: 0.00130 AC XY: 943 AN XY: 726878

African (AFR) AF: 0.0559 AC: 1870 AN: 33468

American (AMR) AF: 0.00246 AC: 110 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5764

European-Non Finnish (NFE) AF: 0.0000855 AC: 95 AN: 1111614

Other (OTH) AF: 0.00359 AC: 217 AN: 60370

GnomAD4 genome AF: 0.0166 AC: 2522 AN: 151986 Hom.: 60 Cov.: 32 AF XY: 0.0152 AC XY: 1130 AN XY: 74318

African (AFR) AF: 0.0584 AC: 2421 AN: 41438

American (AMR) AF: 0.00432 AC: 66 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67924

Other (OTH) AF: 0.00996 AC: 21 AN: 2108

Alfa AF: 0.00603 Hom.: 41

Bravo AF: 0.0180

Asia WGS AF: 0.00289 AC: 11 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		-0.076
Mutation Taster		=21/79	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0016
dbscSNV1_RF	Benign	0.16
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: rs61499963; hg19: chr12-53899633;