Genetic Variant OR52B4:p.Leu41PhefsTer44 (chr11-4368174-AG-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001005161.3(OR52B4):c.121delC(p.Leu41PhefsTer44) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 8167 hom., cov: 0)

Exomes 𝑓: 0.35 ( 91392 hom. )

Consequence

OR52B4
NM_001005161.3 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50

Variant links:

Genes affected

OR52B4 (HGNC:15209): (olfactory receptor family 52 subfamily B 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

OR52B4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 11-4368174-AG-A is Benign according to our data. Variant chr11-4368174-AG-A is described in ClinVar as [Benign]. Clinvar id is 403276.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR52B4	NM_001005161.3 link	c.121delC	p.Leu41PhefsTer44	frameshift_variant	Exon 1 of 1	ENST00000624801.3	NP_001005161.2	Q8NGK2A0A126GW82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR52B4	ENST00000624801.3 link	c.121delC	p.Leu41PhefsTer44	frameshift_variant	Exon 1 of 1	6	NM_001005161.3	ENSP00000485530.1		Q8NGK2

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47433

AN:

151886

Hom.:

8159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.331

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.362

AC:

89982

AN:

248566

Hom.:

17272

AF XY:

0.357

AC XY:

48185

AN XY:

134830

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.496

Gnomad ASJ exome

AF:

0.318

Gnomad EAS exome

AF:

0.436

Gnomad SAS exome

AF:

0.336

Gnomad FIN exome

AF:

0.377

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.362

GnomAD4 exome

AF:

0.349

AC:

510543

AN:

1461118

Hom.:

91392

Cov.:

AF XY:

0.348

AC XY:

252917

AN XY:

726848

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.489

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.373

Gnomad4 NFE exome

AF:

0.348

Gnomad4 OTH exome

AF:

0.348

GnomAD4 genome

AF:

0.312

AC:

47464

AN:

152004

Hom.:

8167

Cov.:

AF XY:

0.318

AC XY:

23603

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.433

Gnomad4 ASJ

AF:

0.330

Gnomad4 EAS

AF:

0.434

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.396

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.329

Alfa

AF:

0.334

Hom.:

1615

Bravo

AF:

0.310

Asia WGS

AF:

0.363

AC:

1261

AN:

3478

EpiCase

AF:

0.336

EpiControl

AF:

0.340

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 716/2178=32.87% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

11-4368174-AGG-AG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over