rs1029239

Positions:

• chr6-30170385-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033229.3(TRIM15):​c.732-116C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 622,646 control chromosomes in the GnomAD database, including 66,323 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 0.44 (15170 hom., cov: 31)
  • Exomes 𝑓: 0.46 (51153 hom.)
• Consequence: TRIM15 NM_033229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202

Genes affected

TRIM15 (HGNC:16284): (tripartite motif containing 15) 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 the cytoplasm. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM15	NM_033229.3	c.732-116C>G		intron_variant		ENST00000376694.9	NP_150232.2
TRIM15	XM_011514987.2	c.417-116C>G		intron_variant			XP_011513289.1
TRIM15	XM_011514988.3	c.111-116C>G		intron_variant			XP_011513290.1
TRIM15	XM_047419503.1	c.718-116C>G		intron_variant			XP_047275459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM15	ENST00000376694.9	c.732-116C>G		intron_variant		1	NM_033229.3	ENSP00000365884	P1
TRIM15	ENST00000433744.1	c.242-116C>G		intron_variant		3		ENSP00000398285
TRIM15	ENST00000619857.4	c.525-116C>G		intron_variant		5		ENSP00000484001
TRIM15	ENST00000477944.1	n.73C>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67231 AN: 151872 Hom.: 15147 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.459 AC: 216158 AN: 470656 Hom.: 51153 Cov.: 6 AF XY: 0.467 AC XY: 115941 AN XY: 248066

Gnomad4 AFR exome AF: 0.434

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.516

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.443 AC: 67287 AN: 151990 Hom.: 15170 Cov.: 31 AF XY: 0.444 AC XY: 32950 AN XY: 74282

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.472

Alfa AF: 0.458 Hom.: 9277

Bravo AF: 0.436

Asia WGS AF: 0.589 AC: 2052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.89
DANN	Benign	0.42

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: rs1029239; hg19: chr6-30138162; COSMIC: COSV64990159;