chr11-5938527-A-C

Variant names:

• chr11-5938527-A-C
• rs3858526
• ENST00000412903.1:c.-334T>G

Variant summary

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

The ENST00000412903.1(TRIM5):​c.-334T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,896 control chromosomes in the GnomAD database, including 7,431 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 0.30 (7431 hom., cov: 31)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TRIM5 ENST00000412903.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 7 publications found

Genes affected

TRIM5 (HGNC:16276): (tripartite motif containing 5) 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 forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

LOC112268071 (HGNC:):

OR56A3 (HGNC:14786): (olfactory receptor family 56 subfamily A member 3) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000412903.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM5	ENST00000412903.1	TSL:1	c.-334T>G		5_prime_UTR	Exon 1 of 5	ENSP00000388031.1
	OR56A3	ENST00000528915.1	TSL:4	n.-224A>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46178 AN: 151766 Hom.: 7413 Cov.: 31

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.250 AC: 3 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 2 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.304 AC: 46240 AN: 151884 Hom.: 7431 Cov.: 31 AF XY: 0.303 AC XY: 22464 AN XY: 74218

African (AFR) AF: 0.402 AC: 16648 AN: 41386

American (AMR) AF: 0.290 AC: 4434 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3466

East Asian (EAS) AF: 0.246 AC: 1260 AN: 5130

South Asian (SAS) AF: 0.241 AC: 1163 AN: 4820

European-Finnish (FIN) AF: 0.292 AC: 3083 AN: 10552

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.264 AC: 17949 AN: 67938

Other (OTH) AF: 0.294 AC: 619 AN: 2108

Alfa AF: 0.271 Hom.: 10486

Bravo AF: 0.308

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		-2.2
PromoterAI		-0.0031	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3858526; hg19: chr11-5959757;