rs2231963

chr11-4603790-A-Cchr11-4603790-A-T

Variant summary

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

The NM_018073.8(TRIM68):c.427-450T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,970 control chromosomes in the GnomAD database, including 13,006 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 0.41 (13006 hom., cov: 32)
• Consequence: TRIM68 NM_018073.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM68	NM_018073.8	c.427-450T>G		intron_variant		ENST00000300747.10
TRIM68	NM_001304496.2	c.-243-450T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM68	ENST00000300747.10	c.427-450T>G		intron_variant		1	NM_018073.8	P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62086 AN: 151852 Hom.: 12990 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.409 AC: 62142 AN: 151970 Hom.: 13006 Cov.: 32 AF XY: 0.405 AC XY: 30104 AN XY: 74280

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.400

Alfa AF: 0.406 Hom.: 2186

Bravo AF: 0.412

Asia WGS AF: 0.369 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	6.3
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2231963; hg19: chr11-4625020;