chr6-30141705-A-G

Variant names:

• chr6-30141705-A-G
• rs9261489
• NM_001286633.2:c.346-4289A>G

Variant summary

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

The NM_001286633.2(TRIM40):​c.346-4289A>G 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 152,184 control chromosomes in the GnomAD database, including 3,090 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 (3090 hom., cov: 32)
• Consequence: TRIM40 NM_001286633.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 22 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM40	NM_001286633.2	c.346-4289A>G		intron_variant	Intron 2 of 5	ENST00000396581.6	NP_001273562.1
TRIM40	NM_138700.4	c.346-4289A>G		intron_variant	Intron 1 of 4		NP_619645.1
TRIM40	XM_011514306.2	c.346-4289A>G		intron_variant	Intron 3 of 6		XP_011512608.1
TRIM40	XM_011514309.2	c.346-4289A>G		intron_variant	Intron 2 of 4		XP_011512611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM40	ENST00000396581.6	c.346-4289A>G		intron_variant	Intron 2 of 5	1	NM_001286633.2	ENSP00000379826.1
TRIM40	ENST00000307859.4	c.346-4289A>G		intron_variant	Intron 1 of 4	1		ENSP00000308310.4
TRIM40	ENST00000376724.6	c.346-4289A>G		intron_variant	Intron 1 of 4	2		ENSP00000365914.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28437 AN: 152066 Hom.: 3086 Cov.: 32

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.289

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: 28463 AN: 152184 Hom.: 3090 Cov.: 32 AF XY: 0.188 AC XY: 13964 AN XY: 74404

African (AFR) AF: 0.0925 AC: 3843 AN: 41538

American (AMR) AF: 0.198 AC: 3036 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3472

East Asian (EAS) AF: 0.243 AC: 1259 AN: 5178

South Asian (SAS) AF: 0.0974 AC: 470 AN: 4824

European-Finnish (FIN) AF: 0.289 AC: 3056 AN: 10576

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

European-Non Finnish (NFE) AF: 0.232 AC: 15757 AN: 67976

Other (OTH) AF: 0.146 AC: 309 AN: 2114

Alfa AF: 0.208 Hom.: 9008

Bravo AF: 0.177

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.85
PhyloP100		-0.42
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: rs9261489; hg19: chr6-30109482;