NM_001005161.3:c.121delC

Variant names:

• chr11-4368174-AG-A
• rs11310407
• NM_001005161.3:c.121delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.50
• Publications: 20 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.121delC	p.Leu41PhefsTer44	frameshift_variant	Exon 1 of 1	ENST00000624801.3	NP_001005161.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47433 AN: 151886 Hom.: 8159 Cov.: 0

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

GnomAD2 exomes AF: 0.362 AC: 89982 AN: 248566 AF XY: 0.357

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 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.: 0 AF XY: 0.348 AC XY: 252917 AN XY: 726848

African (AFR) AF: 0.162 AC: 5407 AN: 33474

American (AMR) AF: 0.489 AC: 21839 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 8413 AN: 26130

East Asian (EAS) AF: 0.421 AC: 16713 AN: 39678

South Asian (SAS) AF: 0.335 AC: 28884 AN: 86238

European-Finnish (FIN) AF: 0.373 AC: 19941 AN: 53392

Middle Eastern (MID) AF: 0.303 AC: 1748 AN: 5768

European-Non Finnish (NFE) AF: 0.348 AC: 386600 AN: 1111454

Other (OTH) AF: 0.348 AC: 20998 AN: 60350

GnomAD4 genome AF: 0.312 AC: 47464 AN: 152004 Hom.: 8167 Cov.: 0 AF XY: 0.318 AC XY: 23603 AN XY: 74272

African (AFR) AF: 0.174 AC: 7199 AN: 41464

American (AMR) AF: 0.433 AC: 6612 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1145 AN: 3470

East Asian (EAS) AF: 0.434 AC: 2242 AN: 5160

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4814

European-Finnish (FIN) AF: 0.396 AC: 4190 AN: 10568

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23526 AN: 67966

Other (OTH) AF: 0.329 AC: 691 AN: 2100

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

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
PhyloP100		-1.5
Mutation Taster		=166/34	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11310407; hg19: chr11-4389404; COSMIC: COSV68768666;