chr11-4602558-T-C

Variant names:

• chr11-4602558-T-C
• rs931811
• NM_018073.8:c.523-146A>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.523-146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,076,770 control chromosomes in the GnomAD database, including 163,828 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 0.48 (18858 hom., cov: 32)
  • Exomes 𝑓: 0.55 (144970 hom.)
• Consequence: TRIM68 NM_018073.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018073.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM68	NM_018073.8	MANE Select	c.523-146A>G		intron	N/A	NP_060543.5
	TRIM68	NM_001304496.2		c.-147-146A>G		intron	N/A	NP_001291425.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM68	ENST00000300747.10	TSL:1 MANE Select	c.523-146A>G		intron	N/A	ENSP00000300747.5	Q6AZZ1-1
	TRIM68	ENST00000855530.1		c.589-146A>G		intron	N/A	ENSP00000525589.1
	TRIM68	ENST00000855531.1		c.553-146A>G		intron	N/A	ENSP00000525590.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72854 AN: 151910 Hom.: 18858 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.555 AC: 513120 AN: 924742 Hom.: 144970 AF XY: 0.558 AC XY: 257501 AN XY: 461516

African (AFR) AF: 0.241 AC: 5196 AN: 21598

American (AMR) AF: 0.577 AC: 12789 AN: 22148

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 9339 AN: 17132

East Asian (EAS) AF: 0.647 AC: 21566 AN: 33316

South Asian (SAS) AF: 0.613 AC: 33772 AN: 55112

European-Finnish (FIN) AF: 0.598 AC: 19851 AN: 33192

Middle Eastern (MID) AF: 0.557 AC: 1607 AN: 2884

European-Non Finnish (NFE) AF: 0.554 AC: 386704 AN: 697722

Other (OTH) AF: 0.535 AC: 22296 AN: 41638

GnomAD4 genome AF: 0.479 AC: 72857 AN: 152028 Hom.: 18858 Cov.: 32 AF XY: 0.488 AC XY: 36269 AN XY: 74306

African (AFR) AF: 0.262 AC: 10864 AN: 41478

American (AMR) AF: 0.566 AC: 8634 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1851 AN: 3472

East Asian (EAS) AF: 0.593 AC: 3051 AN: 5148

South Asian (SAS) AF: 0.600 AC: 2892 AN: 4822

European-Finnish (FIN) AF: 0.601 AC: 6339 AN: 10552

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37630 AN: 67982

Other (OTH) AF: 0.492 AC: 1040 AN: 2112

Alfa AF: 0.529 Hom.: 81175

Bravo AF: 0.464

Asia WGS AF: 0.577 AC: 2004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.3
DANN	Benign	0.69
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs931811; hg19: chr11-4623788;