rs2844775

Positions:

• chr6-30211645-G-A

Variant summary

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

The NM_003449.5(TRIM26):​c.-376+1660C>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 152,094 control chromosomes in the GnomAD database, including 3,450 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 0.20 (3450 hom., cov: 32)
• Consequence: TRIM26 NM_003449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

Genes affected

TRIM26 (HGNC:12962): (tripartite motif containing 26) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. Although the function of the protein is unknown, the RING domain suggests that the protein may have DNA-binding activity. The gene localizes to the major histocompatibility complex (MHC) class I region on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2011]

TRIM26 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM26	NM_003449.5	c.-376+1660C>T		intron_variant		ENST00000454678.7	NP_003440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM26	ENST00000454678.7	c.-376+1660C>T		intron_variant		1	NM_003449.5	ENSP00000410446.2

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29675 AN: 151976 Hom.: 3448 Cov.: 32

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.248

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: 29689 AN: 152094 Hom.: 3450 Cov.: 32 AF XY: 0.197 AC XY: 14675 AN XY: 74348

Gnomad4 AFR AF: 0.0766

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.157

Alfa AF: 0.230 Hom.: 6380

Bravo AF: 0.183

Asia WGS AF: 0.151 AC: 524 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2844775; hg19: chr6-30179422;