rs2857439

Variant names:

• chr6-30138519-G-A
• rs2857439
• NM_001286633.2:c.345+1138G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286633.2(TRIM40):​c.345+1138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,872 control chromosomes in the GnomAD database, including 3,083 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 0.19 (3083 hom., cov: 32)
• Consequence: TRIM40 NM_001286633.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 18 publications found

Genes affected

TRIM40 (HGNC:18736): (tripartite motif containing 40) This gene encodes a member of the tripartite motif (TRIM) protein family. The encoded protein may play a role as a negative regulator against inflammation and carcinogenesis in the gastrointestinal tract. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286633.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM40	NM_001286633.2	MANE Select	c.345+1138G>A		intron	N/A	NP_001273562.1
	TRIM40	NM_138700.4		c.345+1138G>A		intron	N/A	NP_619645.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM40	ENST00000396581.6	TSL:1 MANE Select	c.345+1138G>A		intron	N/A	ENSP00000379826.1
	TRIM40	ENST00000307859.4	TSL:1	c.345+1138G>A		intron	N/A	ENSP00000308310.4
	TRIM40	ENST00000376724.6	TSL:2	c.345+1138G>A		intron	N/A	ENSP00000365914.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28423 AN: 151756 Hom.: 3079 Cov.: 32

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.187 AC: 28449 AN: 151872 Hom.: 3083 Cov.: 32 AF XY: 0.188 AC XY: 13947 AN XY: 74188

African (AFR) AF: 0.0928 AC: 3844 AN: 41440

American (AMR) AF: 0.198 AC: 3028 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3466

East Asian (EAS) AF: 0.244 AC: 1262 AN: 5164

South Asian (SAS) AF: 0.0976 AC: 469 AN: 4806

European-Finnish (FIN) AF: 0.290 AC: 3041 AN: 10504

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15764 AN: 67922

Other (OTH) AF: 0.146 AC: 307 AN: 2106

Alfa AF: 0.206 Hom.: 7205

Bravo AF: 0.177

Asia WGS AF: 0.135 AC: 468 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.49
DANN	Benign	0.21
PhyloP100		-0.082
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2857439; hg19: chr6-30106296;