rs2249099

Positions:

• chr6-30111530-C-A
• chr6-30111530-C-G

Variant summary

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

The NM_007028.5(TRIM31):​c.513+118G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,025,500 control chromosomes in the GnomAD database, including 12,704 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 0.13 (1481 hom., cov: 32)
  • Exomes 𝑓: 0.15 (11223 hom.)
• Consequence: TRIM31 NM_007028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

Genes affected

TRIM31 (HGNC:16289): (tripartite motif containing 31) This gene encodes a protein that functions as an E3 ubiquitin-protein ligase. This gene shows altered expression in certain tumors and may be a negative regulator of cell growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TRIM31-AS1 (HGNC:39761): (TRIM31 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM31	NM_007028.5	c.513+118G>T		intron_variant		ENST00000376734.4
TRIM31-AS1	NR_126470.1	n.274-188C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM31	ENST00000376734.4	c.513+118G>T		intron_variant		5	NM_007028.5	P1
TRIM31-AS1	ENST00000440874.1	n.274-188C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20070 AN: 152036 Hom.: 1471 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.0713

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.153 AC: 133811 AN: 873346 Hom.: 11223 Cov.: 12 AF XY: 0.154 AC XY: 68803 AN XY: 446834

Gnomad4 AFR exome AF: 0.0953

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0883

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.132 AC: 20094 AN: 152154 Hom.: 1481 Cov.: 32 AF XY: 0.131 AC XY: 9747 AN XY: 74366

Gnomad4 AFR AF: 0.0991

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0951

Gnomad4 EAS AF: 0.0705

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.118

Alfa AF: 0.150 Hom.: 1050

Bravo AF: 0.127

Asia WGS AF: 0.192 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	7.0
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2249099; hg19: chr6-30079307; COSMIC: COSV65059400; COSMIC: COSV65059400;