rs2857435

Positions:

• chr6-30138247-A-T

Variant summary

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

The NM_001286633.2(TRIM40):​c.345+866A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,208 control chromosomes in the GnomAD database, including 3,305 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 (3305 hom., cov: 33)
• Consequence: TRIM40 NM_001286633.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM40	NM_001286633.2	c.345+866A>T		intron_variant		ENST00000396581.6
TRIM40	NM_138700.4	c.345+866A>T		intron_variant
TRIM40	XM_011514306.2	c.345+866A>T		intron_variant
TRIM40	XM_011514309.2	c.345+866A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM40	ENST00000396581.6	c.345+866A>T		intron_variant		1	NM_001286633.2	P1
TRIM40	ENST00000307859.4	c.345+866A>T		intron_variant		1
TRIM40	ENST00000376724.6	c.345+866A>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29579 AN: 152090 Hom.: 3296 Cov.: 33

Gnomad AFR AF: 0.0934

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.195 AC: 29614 AN: 152208 Hom.: 3305 Cov.: 33 AF XY: 0.197 AC XY: 14664 AN XY: 74406

Gnomad4 AFR AF: 0.0935

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.163

Alfa AF: 0.218 Hom.: 535

Bravo AF: 0.181

Asia WGS AF: 0.259 AC: 898 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2857435; hg19: chr6-30106024;