rs80227456

Positions:

• chr9-104599170-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001004482.1(OR13C5):​c.244C>T​(p.Leu82Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 142,032 control chromosomes in the GnomAD database, including 18,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (18776 hom., cov: 28)
  • Exomes 𝑓: 0.45 (142549 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR13C5 NM_001004482.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.03

Genes affected

OR13C5 (HGNC:15100): (olfactory receptor family 13 subfamily C member 5) 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]

LOC107987105 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-104599170-G-A is Benign according to our data. Variant chr9-104599170-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 403269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR13C5	NM_001004482.1	c.244C>T	p.Leu82Leu	synonymous_variant	1/1	ENST00000374779.3	NP_001004482.1
LOC107987105	XR_007061705.1	n.427+22860C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR13C5	ENST00000374779.3	c.244C>T	p.Leu82Leu	synonymous_variant	1/1	6	NM_001004482.1	ENSP00000363911.2

Frequencies

GnomAD3 genomes AF: 0.513 AC: 72829 AN: 141916 Hom.: 18758 Cov.: 28

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.473

GnomAD3 exomes AF: 0.475 AC: 96815 AN: 203832 Hom.: 26738 AF XY: 0.460 AC XY: 50421 AN XY: 109684

Gnomad AFR exome AF: 0.629

Gnomad AMR exome AF: 0.615

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.910

Gnomad SAS exome AF: 0.463

Gnomad FIN exome AF: 0.450

Gnomad NFE exome AF: 0.371

Gnomad OTH exome AF: 0.422

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.454 AC: 652646 AN: 1439004 Hom.: 142549 Cov.: 39 AF XY: 0.454 AC XY: 325276 AN XY: 716400

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.623

Gnomad4 ASJ exome AF: 0.340

Gnomad4 EAS exome AF: 0.924

Gnomad4 SAS exome AF: 0.513

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.513 AC: 72904 AN: 142032 Hom.: 18776 Cov.: 28 AF XY: 0.518 AC XY: 35942 AN XY: 69396

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.476

Alfa AF: 0.509 Hom.: 2164

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs80227456; hg19: chr9-107361451; COSMIC: COSV66164092;