chr11-4603790-A-C

Variant names:

• chr11-4603790-A-C
• rs2231963
• NM_018073.8:c.427-450T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRIM68	NM_018073.8	c.427-450T>G		intron_variant	Intron 2 of 6	ENST00000300747.10	NP_060543.5
TRIM68	NM_001304496.2	c.-243-450T>G		intron_variant	Intron 1 of 5		NP_001291425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM68	ENST00000300747.10	c.427-450T>G		intron_variant	Intron 2 of 6	1	NM_018073.8	ENSP00000300747.5

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

African (AFR) AF: 0.490 AC: 20290 AN: 41420

American (AMR) AF: 0.364 AC: 5555 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1055 AN: 3458

East Asian (EAS) AF: 0.367 AC: 1896 AN: 5168

South Asian (SAS) AF: 0.378 AC: 1818 AN: 4812

European-Finnish (FIN) AF: 0.358 AC: 3778 AN: 10550

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26416 AN: 67968

Other (OTH) AF: 0.400 AC: 843 AN: 2110

Alfa AF: 0.423 Hom.: 5898

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
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2231963; hg19: chr11-4625020;