chr11-5755396-C-T

Position:

• chr11-5755396-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001005175.5(OR52N4):​c.656C>T​(p.Ser219Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00827 in 1,613,994 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (61 hom.)
• Consequence: OR52N4 NM_001005175.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.96

Genes affected

OR52N4 (HGNC:15230): (olfactory receptor family 52 subfamily N 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.041511774).
• BP6: Variant 11-5755396-C-T is Benign according to our data. Variant chr11-5755396-C-T is described in ClinVar as [Benign]. Clinvar id is 782293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR52N4	NM_001005175.5	c.656C>T	p.Ser219Phe	missense_variant	2/2	ENST00000641350.2
OR52N4	XM_017017711.3	c.656C>T	p.Ser219Phe	missense_variant	5/5
OR52N4	XM_017017713.3	c.656C>T	p.Ser219Phe	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52N4	ENST00000641350.2	c.656C>T	p.Ser219Phe	missense_variant	2/2		NM_001005175.5	P1
TRIM5	ENST00000412903.1	c.-61-75158G>A		intron_variant		1
TRIM5	ENST00000380027.5	c.-440-70002G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00624 AC: 950 AN: 152148 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00617 AC: 1538 AN: 249446 Hom.: 6 AF XY: 0.00605 AC XY: 819 AN XY: 135266

Gnomad AFR exome AF: 0.000708

Gnomad AMR exome AF: 0.00330

Gnomad ASJ exome AF: 0.00637

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000621

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.00941

Gnomad OTH exome AF: 0.00645

GnomAD4 exome AF: 0.00849 AC: 12403 AN: 1461728 Hom.: 61 Cov.: 36 AF XY: 0.00835 AC XY: 6069 AN XY: 727162

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00324

Gnomad4 ASJ exome AF: 0.00631

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000580

Gnomad4 FIN exome AF: 0.00953

Gnomad4 NFE exome AF: 0.00992

Gnomad4 OTH exome AF: 0.00752

GnomAD4 genome AF: 0.00624 AC: 950 AN: 152266 Hom.: 3 Cov.: 32 AF XY: 0.00613 AC XY: 456 AN XY: 74448

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00847

Gnomad4 NFE AF: 0.0105

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00849 Hom.: 8

Bravo AF: 0.00529

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.000929 AC: 4

ESP6500EA AF: 0.00806 AC: 69

ExAC AF: 0.00570 AC: 691

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00905

EpiControl AF: 0.00895

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0059	T;T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.042	T;T
MetaSVM	Uncertain	0.040	D
MutationAssessor	Pathogenic	3.9	H;H
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.34	T
Polyphen		1.0	D;D
Vest4		0.70
MVP		0.79
MPC		0.13
ClinPred		0.085	T
GERP RS		6.1
Varity_R		0.91
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs142159415; hg19: chr11-5776626;