rs4971100

chr1-155183255-G-Achr1-155183255-G-C

Variant summary

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

The NM_025058.5(TRIM46):c.1887-542G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,620 control chromosomes in the GnomAD database, including 13,269 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 0.40 (13269 hom., cov: 29)
• Consequence: TRIM46 NM_025058.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

Genes affected

TRIM46 (HGNC:19019): (tripartite motif containing 46) This gene encodes a protein of the tripartite motif (TRIM) family. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. TRIM46 is reported to be involved in the proliferation of multiple types of cancer cells including lung and breast cancer. It has also been shown to control neuronal polarity and axon specification by forming uniform microtubule bundles in the axon. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM46	NM_025058.5	c.1887-542G>A		intron_variant		ENST00000334634.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM46	ENST00000334634.9	c.1887-542G>A		intron_variant		1	NM_025058.5	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60916 AN: 151502 Hom.: 13273 Cov.: 29

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.402 AC: 60920 AN: 151620 Hom.: 13269 Cov.: 29 AF XY: 0.411 AC XY: 30421 AN XY: 74066

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.414

Alfa AF: 0.426 Hom.: 9393

Bravo AF: 0.404

Asia WGS AF: 0.543 AC: 1890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.56
Dann	Benign	0.74

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: rs4971100; hg19: chr1-155155731;