chr1-234466956-T-A

Position:

• chr1-234466956-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

TARBP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TARBP1	NM_005646.4	c.1248+546A>T		intron_variant		ENST00000040877.2	NP_005637.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TARBP1	ENST00000040877.2	c.1248+546A>T		intron_variant		1	NM_005646.4	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

Gnomad4 AFR AF: 0.0880

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0932

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0789

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs16843250; hg19: chr1-234602702;