rs9261491

Positions:

• chr6-30142084-A-C

Variant summary

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

The NM_001286633.2(TRIM40):​c.346-3910A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,932 control chromosomes in the GnomAD database, including 4,015 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 0.22 (4015 hom., cov: 31)
• Consequence: TRIM40 NM_001286633.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM40	NM_001286633.2	c.346-3910A>C		intron_variant		ENST00000396581.6	NP_001273562.1
TRIM40	NM_138700.4	c.346-3910A>C		intron_variant			NP_619645.1
TRIM40	XM_011514306.2	c.346-3910A>C		intron_variant			XP_011512608.1
TRIM40	XM_011514309.2	c.346-3910A>C		intron_variant			XP_011512611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM40	ENST00000396581.6	c.346-3910A>C		intron_variant		1	NM_001286633.2	ENSP00000379826.1
TRIM40	ENST00000307859.4	c.346-3910A>C		intron_variant		1		ENSP00000308310.4
TRIM40	ENST00000376724.6	c.346-3910A>C		intron_variant		2		ENSP00000365914.2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33401 AN: 151812 Hom.: 4013 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.220 AC: 33421 AN: 151932 Hom.: 4015 Cov.: 31 AF XY: 0.221 AC XY: 16437 AN XY: 74250

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.189

Alfa AF: 0.236 Hom.: 1728

Bravo AF: 0.212

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.68
DANN	Benign	0.38

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: rs9261491; hg19: chr6-30109861;