Genetic Variant TRIM61:c.526-2087T>C (chr4-164957183-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001012414.3(TRIM61):c.526-2087T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,612,466 control chromosomes in the GnomAD database, including 32,044 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 0.16 ( 2804 hom., cov: 32)

Exomes 𝑓: 0.18 ( 29240 hom. )

Consequence

TRIM61
NM_001012414.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72

Publications

38 publications found

Variant links:

Genes affected

TRIM61 (HGNC:24339): (tripartite motif containing 61) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM61 links:

FAM218A (HGNC:26466): (family with sequence similarity 218 member A)

FAM218A 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 (MetaRNN=7.5631556E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012414.3. 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
	TRIM61	NM_001012414.3		c.526-2087T>C		intron	N/A	NP_001012414.1	Q5EBN2
	FAM218A	NR_160935.1		n.236A>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM61	ENST00000329314.6	TSL:1	c.526-2087T>C		intron	N/A	ENSP00000332288.5	Q5EBN2
	FAM218A	ENST00000648094.2		n.238A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24233

AN:

152016

Hom.:

2801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0802

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.196

GnomAD2 exomes

AF:

0.219

AC:

54324

AN:

247604

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.0791

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.615

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.179

AC:

261179

AN:

1460332

Hom.:

29240

Cov.:

AF XY:

0.184

AC XY:

133513

AN XY:

726338

show subpopulations

African (AFR)

AF:

0.0772

AC:

2583

AN:

33464

American (AMR)

AF:

0.221

AC:

9825

AN:

44446

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

5216

AN:

26128

East Asian (EAS)

AF:

0.596

AC:

23603

AN:

39618

South Asian (SAS)

AF:

0.335

AC:

28846

AN:

86038

European-Finnish (FIN)

AF:

0.156

AC:

8314

AN:

53184

Middle Eastern (MID)

AF:

0.256

AC:

1474

AN:

5762

European-Non Finnish (NFE)

AF:

0.152

AC:

169132

AN:

1111386

Other (OTH)

AF:

0.202

AC:

12186

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

13244

26488

39732

52976

66220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6312

12624

18936

25248

31560

<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:

0.159

AC:

24245

AN:

152134

Hom.:

2804

Cov.:

AF XY:

0.164

AC XY:

12228

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0802

AC:

3329

AN:

41518

American (AMR)

AF:

0.171

AC:

2616

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

638

AN:

3466

East Asian (EAS)

AF:

0.612

AC:

3155

AN:

5156

South Asian (SAS)

AF:

0.370

AC:

1784

AN:

4816

European-Finnish (FIN)

AF:

0.150

AC:

1585

AN:

10580

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10575

AN:

67992

Other (OTH)

AF:

0.203

AC:

430

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

971

1941

2912

3882

4853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.167

Hom.:

10230

Bravo

AF:

0.160

TwinsUK

AF:

0.148

AC:

547

ALSPAC

AF:

0.142

AC:

549

ESP6500AA

AF:

0.0790

AC:

348

ESP6500EA

AF:

0.151

AC:

1298

ExAC

AF:

0.212

AC:

25701

Asia WGS

AF:

0.495

AC:

1720

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.0

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.045

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0000076

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

-1.7

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.074

Polyphen

0.048

Vest4

0.011

MPC

0.91

ClinPred

0.0024

GERP RS

-1.1

Varity_R

0.23

gMVP

0.010

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over