dbSNP rs11033006: TRIM68:c.-57-119G>A (chr11-4605680-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.351

Publications

2 publications found

Variant links:

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]

TRIM68 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TRIM68	NM_018073.8 link	c.-57-119G>A		intron_variant	Intron 1 of 6	ENST00000300747.10	NP_060543.5
TRIM68	NM_001304496.2 link	c.-243-2340G>A		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 link	c.-57-119G>A		intron_variant	Intron 1 of 6	1	NM_018073.8	ENSP00000300747.5

Frequencies

GnomAD3 genomes

AF:

0.0228

AC:

3473

AN:

152058

Hom.:

138

Cov.:

show subpopulations

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.:

AF XY:

0.00294

AC XY:

779

AN XY:

265356

show subpopulations

African (AFR)

AF:

0.0765

AC:

1039

AN:

13576

American (AMR)

AF:

0.00569

AC:

105

AN:

18438

Ashkenazi Jewish (ASJ)

AF:

0.00236

AC:

AN:

13968

East Asian (EAS)

AF:

0.00

AC:

AN:

31136

South Asian (SAS)

AF:

0.00114

AC:

AN:

44646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29008

Middle Eastern (MID)

AF:

0.00932

AC:

AN:

2146

European-Non Finnish (NFE)

AF:

0.000899

AC:

296

AN:

329368

Other (OTH)

AF:

0.00722

AC:

201

AN:

27844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

163

245

326

408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0229

AC:

3485

AN:

152176

Hom.:

140

Cov.:

AF XY:

0.0223

AC XY:

1659

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0788

AC:

3271

AN:

41492

American (AMR)

AF:

0.00693

AC:

106

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68008

Other (OTH)

AF:

0.0161

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

167

333

500

666

833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0246

Asia WGS

AF:

0.00635

AC:

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

(source)

DANN

Benign

0.59

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over