NM_005646.4:c.1248+546A>T

Variant names:

• chr1-234466956-T-A
• rs16843250
• NM_005646.4:c.1248+546A>T

Variant summary

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

The NM_005646.4(TARBP1):​c.1248+546A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 152,282 control chromosomes in the GnomAD database, including 923 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 0.084 (923 hom., cov: 32)
• Consequence: TARBP1 NM_005646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005646.4. 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
	TARBP1	NM_005646.4	MANE Select	c.1248+546A>T		intron	N/A	NP_005637.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TARBP1	ENST00000040877.2	TSL:1 MANE Select	c.1248+546A>T		intron	N/A	ENSP00000040877.1

Frequencies

GnomAD3 genomes AF: 0.0834 AC: 12698 AN: 152164 Hom.: 914 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0764

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

GnomAD4 genome AF: 0.0836 AC: 12730 AN: 152282 Hom.: 923 Cov.: 32 AF XY: 0.0903 AC XY: 6722 AN XY: 74448

African (AFR) AF: 0.0880 AC: 3657 AN: 41564

American (AMR) AF: 0.183 AC: 2793 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3470

East Asian (EAS) AF: 0.272 AC: 1406 AN: 5176

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4826

European-Finnish (FIN) AF: 0.0932 AC: 989 AN: 10610

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0358 AC: 2432 AN: 68014

Other (OTH) AF: 0.0789 AC: 167 AN: 2116

Alfa AF: 0.0572 Hom.: 54

Bravo AF: 0.0881

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.73
PhyloP100		0.56
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: rs16843250; hg19: chr1-234602702;