11-8068452-T-C

Position:

• chr11-8068452-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_120537.1(TUB-AS1):​n.1100T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,160 control chromosomes in the GnomAD database, including 16,271 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 0.46 (16244 hom., cov: 32)
  • Exomes 𝑓: 0.48 (27 hom.)
• Consequence: TUB-AS1 NR_120537.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434

Genes affected

TUB (HGNC:12406): (TUB bipartite transcription factor) This gene encodes a member of the Tubby family of bipartite transcription factors. The encoded protein may play a role in obesity and sensorineural degradation. The crystal structure has been determined for a similar protein in mouse, and it functions as a membrane-bound transcription regulator that translocates to the nucleus in response to phosphoinositide hydrolysis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

TUB-AS1 (HGNC:51120): (TUB antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUB-AS1	NR_120537.1	n.1100T>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUB	ENST00000305253.8	c.204-21158T>C		intron_variant		1		ENSP00000305426
TUB-AS1	ENST00000506601.1	n.1100T>C		non_coding_transcript_exon_variant	4/4	2
TUB	ENST00000534099.5	c.57-21158T>C		intron_variant		2		ENSP00000434400

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69383 AN: 151830 Hom.: 16241 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.481 AC: 102 AN: 212 Hom.: 27 Cov.: 0 AF XY: 0.473 AC XY: 69 AN XY: 146

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.457 AC: 69405 AN: 151948 Hom.: 16244 Cov.: 32 AF XY: 0.451 AC XY: 33500 AN XY: 74260

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.418

Alfa AF: 0.437 Hom.: 30055

Bravo AF: 0.452

Asia WGS AF: 0.446 AC: 1549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7114039; hg19: chr11-8089999;