rs11033006

Positions:

• chr11-4605680-C-T

Variant summary

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

The NM_018073.8(TRIM68):​c.-57-119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0079 in 662,306 control chromosomes in the GnomAD database, including 187 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 0.023 (140 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (47 hom.)
• Consequence: TRIM68 NM_018073.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

Genes affected

TRIM68 (HGNC:21161): (tripartite motif containing 68) This gene encodes a member of the tripartite motif-containing protein family, whose members are characterized by a "really interesting new gene" (RING) finger domain, a zinc-binding B-box motif, and a coiled-coil region. Members of this family function as E3 ubiquitin ligases and are involved in a broad range of biological processes. This gene regulates the activation of nuclear receptors, such as androgen receptor, and has been implicated in development of prostate cancer cells, where its expression increases in response to a downregulation of microRNAs. In addition, this gene participates in viral defense regulation as a negative regulator of interferon-beta. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM68	NM_018073.8	c.-57-119G>A		intron_variant		ENST00000300747.10
TRIM68	NM_001304496.2	c.-243-2340G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM68	ENST00000300747.10	c.-57-119G>A		intron_variant		1	NM_018073.8	P1

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3473 AN: 152058 Hom.: 138 Cov.: 33

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00342 AC: 1745 AN: 510130 Hom.: 47 AF XY: 0.00294 AC XY: 779 AN XY: 265356

Gnomad4 AFR exome AF: 0.0765

Gnomad4 AMR exome AF: 0.00569

Gnomad4 ASJ exome AF: 0.00236

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00114

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000899

Gnomad4 OTH exome AF: 0.00722

GnomAD4 genome AF: 0.0229 AC: 3485 AN: 152176 Hom.: 140 Cov.: 33 AF XY: 0.0223 AC XY: 1659 AN XY: 74378

Gnomad4 AFR AF: 0.0788

Gnomad4 AMR AF: 0.00693

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000823

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0146 Hom.: 20

Bravo AF: 0.0246

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.59

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: rs11033006; hg19: chr11-4626910;