NM_003449.5:c.765+1484T>C

Variant names:

• chr6-30195032-A-G
• rs4711211
• NM_003449.5:c.765+1484T>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.765+1484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,114 control chromosomes in the GnomAD database, including 2,875 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 (2875 hom., cov: 32)
• Consequence: TRIM26 NM_003449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 31 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 (NFE) allele frequency at 95% confidence interval = 0.23 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.765+1484T>C		intron	N/A	NP_003440.1
	TRIM26	NM_001242783.2		c.765+1484T>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.765+1484T>C		intron	N/A	ENSP00000410446.2
	TRIM26	ENST00000437089.5	TSL:1	c.765+1484T>C		intron	N/A	ENSP00000395491.1
	TRIM26	ENST00000453195.5	TSL:1	c.765+1484T>C		intron	N/A	ENSP00000391879.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26186 AN: 151994 Hom.: 2873 Cov.: 32

Gnomad AFR AF: 0.0451

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.172 AC: 26197 AN: 152114 Hom.: 2875 Cov.: 32 AF XY: 0.173 AC XY: 12899 AN XY: 74350

African (AFR) AF: 0.0451 AC: 1871 AN: 41504

American (AMR) AF: 0.190 AC: 2904 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3466

East Asian (EAS) AF: 0.208 AC: 1076 AN: 5176

South Asian (SAS) AF: 0.0956 AC: 461 AN: 4824

European-Finnish (FIN) AF: 0.293 AC: 3097 AN: 10562

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15811 AN: 67972

Other (OTH) AF: 0.131 AC: 276 AN: 2112

Alfa AF: 0.207 Hom.: 14436

Bravo AF: 0.160

Asia WGS AF: 0.132 AC: 460 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	1.7
DANN	Benign	0.78
PhyloP100		-0.17
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: rs4711211; hg19: chr6-30162809;