1-11013450-TCA-T

Position:

• chr1-11013450-TCA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007375.4(TARDBP):​c.-12-263_-12-262del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (39479 hom., cov: 0)
• Consequence: TARDBP NM_007375.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0270

Genes affected

TARDBP (HGNC:11571): (TAR DNA binding protein) 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 is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. A similar pseudogene is present on chromosome 20. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-11013450-TCA-T is Benign according to our data. Variant chr1-11013450-TCA-T is described in ClinVar as [Benign]. Clinvar id is 1237929.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-11013450-TCA-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TARDBP	NM_007375.4	c.-12-263_-12-262del		intron_variant		ENST00000240185.8	NP_031401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TARDBP	ENST00000240185.8	c.-12-263_-12-262del		intron_variant		1	NM_007375.4	ENSP00000240185	P1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104661 AN: 151890 Hom.: 39469 Cov.: 0

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.689 AC: 104708 AN: 152010 Hom.: 39479 Cov.: 0 AF XY: 0.691 AC XY: 51368 AN XY: 74318

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.739

Alfa AF: 0.748 Hom.: 5456

Bravo AF: 0.671

Asia WGS AF: 0.782 AC: 2718 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs58761409; hg19: chr1-11073507;