rs17277546

Positions:

• chr7-99891948-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 109 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM4	NM_033091.3	c.*215C>T		3_prime_UTR_variant	6/6	ENST00000349062.7
TRIM4	NM_033017.4	c.*215C>T		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM4	ENST00000349062.7	c.*215C>T		3_prime_UTR_variant	6/6	1	NM_033091.3	P2
TRIM4	ENST00000355947.6	c.*215C>T		3_prime_UTR_variant	7/7	1		A2
TRIM4	ENST00000447480.5	c.545+11270C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4750 AN: 152140 Hom.: 108 Cov.: 32

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.: 4 AF XY: 0.0372 AC XY: 6365 AN XY: 170896

Gnomad4 AFR exome AF: 0.00922

Gnomad4 AMR exome AF: 0.0235

Gnomad4 ASJ exome AF: 0.0182

Gnomad4 EAS exome AF: 0.0000746

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.0584

Gnomad4 NFE exome AF: 0.0446

Gnomad4 OTH exome AF: 0.0313

GnomAD4 genome AF: 0.0312 AC: 4749 AN: 152258 Hom.: 109 Cov.: 32 AF XY: 0.0309 AC XY: 2300 AN XY: 74448

Gnomad4 AFR AF: 0.00825

Gnomad4 AMR AF: 0.0289

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.0596

Gnomad4 NFE AF: 0.0455

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0418 Hom.: 339

Bravo AF: 0.0279

Asia WGS AF: 0.0100 AC: 35 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
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs17277546; hg19: chr7-99489571;