dbSNP rs17277546: TRIM4:c.*215C>T (chr7-99891948-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_033091.3(TRIM4):c.*215C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 485,818 control chromosomes in the GnomAD database, including 395 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 0.031 ( 109 hom., cov: 32)

Exomes 𝑓: 0.037 ( 286 hom. )

Consequence

TRIM4
NM_033091.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.202

Publications

30 publications found

Variant links:

Genes affected

TRIM4 (HGNC:16275): (tripartite motif containing 4) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. Its function has not been identified. Alternatively spliced transcript variants that encode different isoforms have been described.[provided by RefSeq, Jul 2010]

TRIM4 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=-0.78).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0312 (4749/152258) while in subpopulation NFE AF = 0.0455 (3093/68008). AF 95% confidence interval is 0.0441. There are 109 homozygotes in GnomAd4. There are 2300 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 109 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM4	NM_033091.3 link	c.*215C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000349062.7	NP_149082.1	Q9C037-2
TRIM4	NM_033017.4 link	c.*215C>T		3_prime_UTR_variant	Exon 7 of 7		NP_148977.2	Q9C037-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIM4	ENST00000349062.7 link	c.*215C>T	3_prime_UTR_variant	Exon 6 of 6	1	NM_033091.3	ENSP00000275736.4	Q9C037-2
TRIM4	ENST00000355947.6 link	c.*215C>T	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000348216.2	Q9C037-1
TRIM4	ENST00000447480.5 link	c.544+11270C>T	intron_variant	Intron 5 of 5	3		ENSP00000396229.1	H7C0Q6

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

4750

AN:

152140

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00828

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0291

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0596

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0455

Gnomad OTH

AF:

0.0320

GnomAD4 exome

AF:

0.0371

AC:

12372

AN:

333560

Hom.:

286

Cov.:

AF XY:

0.0372

AC XY:

6365

AN XY:

170896

show subpopulations

African (AFR)

AF:

0.00922

AC:

AN:

10518

American (AMR)

AF:

0.0235

AC:

262

AN:

11142

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

203

AN:

11174

East Asian (EAS)

AF:

0.0000746

AC:

AN:

26808

South Asian (SAS)

AF:

0.0181

AC:

304

AN:

16800

European-Finnish (FIN)

AF:

0.0584

AC:

1430

AN:

24472

Middle Eastern (MID)

AF:

0.0245

AC:

AN:

1554

European-Non Finnish (NFE)

AF:

0.0446

AC:

9393

AN:

210566

Other (OTH)

AF:

0.0313

AC:

643

AN:

20526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

561

1121

1682

2242

2803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.0312

AC:

4749

AN:

152258

Hom.:

109

Cov.:

AF XY:

0.0309

AC XY:

2300

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00825

AC:

343

AN:

41564

American (AMR)

AF:

0.0289

AC:

442

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0176

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0596

AC:

632

AN:

10598

Middle Eastern (MID)

AF:

0.0240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0455

AC:

3093

AN:

68008

Other (OTH)

AF:

0.0317

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

234

468

702

936

1170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0406

Hom.:

642

Bravo

AF:

0.0279

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.0

(source)

DANN

Benign

0.76

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(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