NM_005646.4:c.1961+608G>A

Variant names:

• chr1-234447872-C-T
• rs10489896
• NM_005646.4:c.1961+608G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005646.4(TARBP1):​c.1961+608G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,920 control chromosomes in the GnomAD database, including 6,811 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 0.30 (6811 hom., cov: 32)
• Consequence: TARBP1 NM_005646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 10 publications found

Genes affected

TARBP1 (HGNC:11568): (TAR (HIV-1) RNA binding protein 1) 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. This element forms a stable stem-loop structure and can be bound by either the protein encoded by this gene or by RNA polymerase II. This protein may act to disengage RNA polymerase II from TAR during transcriptional elongation. Alternatively spliced transcripts of this gene may exist, but their full-length natures have not been determined. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TARBP1	NM_005646.4	c.1961+608G>A		intron_variant	Intron 11 of 29	ENST00000040877.2	NP_005637.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TARBP1	ENST00000040877.2	c.1961+608G>A		intron_variant	Intron 11 of 29	1	NM_005646.4	ENSP00000040877.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44852 AN: 151802 Hom.: 6802 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44888 AN: 151920 Hom.: 6811 Cov.: 32 AF XY: 0.301 AC XY: 22372 AN XY: 74232

African (AFR) AF: 0.293 AC: 12133 AN: 41396

American (AMR) AF: 0.402 AC: 6142 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 966 AN: 3470

East Asian (EAS) AF: 0.319 AC: 1643 AN: 5154

South Asian (SAS) AF: 0.262 AC: 1261 AN: 4820

European-Finnish (FIN) AF: 0.306 AC: 3224 AN: 10520

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18521 AN: 67956

Other (OTH) AF: 0.316 AC: 667 AN: 2114

Alfa AF: 0.281 Hom.: 11371

Bravo AF: 0.304

Asia WGS AF: 0.271 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.029
DANN	Benign	0.22
PhyloP100		-2.7
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: rs10489896; hg19: chr1-234583618;