rs2021723

Positions:

• chr6-30136146-G-A

Variant summary

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

The NM_001286633.2(TRIM40):​c.-348G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,204 control chromosomes in the GnomAD database, including 2,608 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 0.17 (2608 hom., cov: 32)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: TRIM40 NM_001286633.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM40	NM_001286633.2	c.-348G>A		5_prime_UTR_variant	1/6	ENST00000396581.6	NP_001273562.1
TRIM40	XM_011514306.2	c.-535G>A		5_prime_UTR_variant	1/7		XP_011512608.1
TRIM40	XM_011514309.2	c.-669G>A		5_prime_UTR_variant	1/5		XP_011512611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM40	ENST00000396581.6	c.-348G>A		5_prime_UTR_variant	1/6	1	NM_001286633.2	ENSP00000379826	P1
TRIM40	ENST00000489892.1	n.23G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25647 AN: 152040 Hom.: 2605 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.109 AC: 5 AN: 46 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 4 AN XY: 32

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0357

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.169 AC: 25677 AN: 152158 Hom.: 2608 Cov.: 32 AF XY: 0.166 AC XY: 12328 AN XY: 74406

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0354

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.197

Alfa AF: 0.140 Hom.: 2786

Bravo AF: 0.188

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2021723; hg19: chr6-30103923;