11-5755396-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.96

Publications

8 publications found

Variant links:

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]

OR52N4 links:

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]

TRIM5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 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 VariationId is 782293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005175.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52N4	NM_001005175.5	MANE Select	c.656C>T	p.Ser219Phe	missense	Exon 2 of 2	NP_001005175.3	Q8NGI2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR52N4	ENST00000641350.2	MANE Select	c.656C>T	p.Ser219Phe	missense	Exon 2 of 2	ENSP00000493338.1	Q8NGI2
TRIM5	ENST00000412903.1	TSL:1	c.-61-75158G>A		intron	N/A	ENSP00000388031.1	E7EQQ5
TRIM5	ENST00000957480.1		c.-62+53503G>A		intron	N/A	ENSP00000627539.1

Frequencies

GnomAD3 genomes

AF:

0.00624

AC:

950

AN:

152148

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00617

AC:

1538

AN:

249446

AF XY:

0.00605

show subpopulations

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 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.:

Cov.:

AF XY:

0.00835

AC XY:

6069

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

33472

American (AMR)

AF:

0.00324

AC:

145

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00631

AC:

165

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.000580

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00953

AC:

509

AN:

53418

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00992

AC:

11028

AN:

1111918

Other (OTH)

AF:

0.00752

AC:

454

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

812

1624

2436

3248

4060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

410

820

1230

1640

2050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00624

AC:

950

AN:

152266

Hom.:

Cov.:

AF XY:

0.00613

AC XY:

456

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00166

AC:

AN:

41544

American (AMR)

AF:

0.00294

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00847

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0105

AC:

716

AN:

68024

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00839

Hom.:

Bravo

AF:

0.00529

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.000929

AC:

ESP6500EA

AF:

0.00806

AC:

ExAC

AF:

0.00570

AC:

691

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00895

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0059

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.057

MetaRNN

Benign

0.042

MetaSVM

Uncertain

0.040

MutationAssessor

Pathogenic

3.9

PhyloP100

4.0

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.70

MVP

0.79

MPC

0.13

ClinPred

0.085

GERP RS

6.1

Varity_R

0.91

gMVP

0.55

Mutation Taster

=19/81

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over