rs2286748

Positions:

• chr10-102654952-C-A
• chr10-102654952-C-T

Variant summary

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

The NM_030912.3(TRIM8):​c.667-128C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,140,794 control chromosomes in the GnomAD database, including 54,852 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 0.30 (6871 hom., cov: 32)
  • Exomes 𝑓: 0.31 (47981 hom.)
• Consequence: TRIM8 NM_030912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

Genes affected

TRIM8 (HGNC:15579): (tripartite motif containing 8) This gene encodes a member of the tripartite motif (TRIM) protein family. Based on similarities to other proteins, the encoded protein is suspected to be an E3 ubiquitin-protein ligase. Regulation of this gene may be altered in some cancers. Mutations resulting in a truncated protein product have been observed in early-onset epileptic encephalopathy (EOEE). [provided by RefSeq, Sep 2016]

LOC105378460 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM8	NM_030912.3	c.667-128C>A		intron_variant		ENST00000643721.2
LOC105378460	XR_007062272.1	n.85+95G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM8	ENST00000643721.2	c.667-128C>A		intron_variant			NM_030912.3	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45525 AN: 151968 Hom.: 6869 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.308 AC: 304569 AN: 988708 Hom.: 47981 Cov.: 13 AF XY: 0.311 AC XY: 156801 AN XY: 504396

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.445

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.300 AC: 45559 AN: 152086 Hom.: 6871 Cov.: 32 AF XY: 0.299 AC XY: 22190 AN XY: 74326

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.321

Alfa AF: 0.282 Hom.: 736

Bravo AF: 0.298

Asia WGS AF: 0.345 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2286748; hg19: chr10-104414709; COSMIC: COSV56660110; COSMIC: COSV56660110;