6-30201550-A-G

Variant names:

• chr6-30201550-A-G
• rs2517611
• NM_003449.5:c.-265-412T>C

Variant summary

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

The NM_003449.5(TRIM26):​c.-265-412T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,128 control chromosomes in the GnomAD database, including 4,225 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 (4225 hom., cov: 32)
• Consequence: TRIM26 NM_003449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 38 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003449.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM26	NM_003449.5	MANE Select	c.-265-412T>C		intron	N/A	NP_003440.1
	TRIM26	NM_001242783.2		c.-154-412T>C		intron	N/A	NP_001229712.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM26	ENST00000454678.7	TSL:1 MANE Select	c.-265-412T>C		intron	N/A	ENSP00000410446.2
	TRIM26	ENST00000437089.5	TSL:1	c.-99-467T>C		intron	N/A	ENSP00000395491.1
	TRIM26	ENST00000453195.5	TSL:1	c.-154-412T>C		intron	N/A	ENSP00000391879.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33595 AN: 152010 Hom.: 4206 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0826

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.221 AC: 33666 AN: 152128 Hom.: 4225 Cov.: 32 AF XY: 0.213 AC XY: 15876 AN XY: 74372

African (AFR) AF: 0.332 AC: 13755 AN: 41450

American (AMR) AF: 0.181 AC: 2775 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3472

East Asian (EAS) AF: 0.0830 AC: 430 AN: 5180

South Asian (SAS) AF: 0.156 AC: 754 AN: 4830

European-Finnish (FIN) AF: 0.101 AC: 1066 AN: 10594

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13543 AN: 67992

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.208 Hom.: 13045

Bravo AF: 0.235

Asia WGS AF: 0.138 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.9
DANN	Benign	0.41
PhyloP100		-0.020
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2517611; hg19: chr6-30169327;