rs1377518

Positions:

• chr11-5880722-T-C
• chr11-5880722-T-G

Variant summary

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

The NM_001005165.2(OR52E4):​c.-75+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,064 control chromosomes in the GnomAD database, including 11,855 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 0.39 (11847 hom., cov: 32)
  • Exomes 𝑓: 0.41 (8 hom.)
• Consequence: OR52E4 NM_001005165.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

Genes affected

OR52E4 (HGNC:15213): (olfactory receptor family 52 subfamily E member 4) 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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR52E4	NM_001005165.2	c.-75+8T>C		splice_region_variant, intron_variant		ENST00000641726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52E4	ENST00000641726.1	c.-75+8T>C		splice_region_variant, intron_variant			NM_001005165.2	P1
TRIM5	ENST00000412903.1	c.-62+56679A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59294 AN: 151870 Hom.: 11843 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.408 AC: 31 AN: 76 Hom.: 8 Cov.: 0 AF XY: 0.394 AC XY: 26 AN XY: 66

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.390 AC: 59322 AN: 151988 Hom.: 11847 Cov.: 32 AF XY: 0.389 AC XY: 28876 AN XY: 74258

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.386

Alfa AF: 0.415 Hom.: 6525

Bravo AF: 0.383

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1377518; hg19: chr11-5901952;