rs80227456

Variant names:

• chr9-104599170-G-A
• rs80227456
• NM_001004482.1:c.244C>T

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. L82L) has been classified 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OR13C5	NM_001004482.1	c.244C>T	p.Leu82Leu	synonymous_variant	Exon 1 of 1	ENST00000374779.3	NP_001004482.1
LOC107987105	XR_007061705.1	n.427+22860C>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR13C5	ENST00000374779.3	c.244C>T	p.Leu82Leu	synonymous_variant	Exon 1 of 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

GnomAD2 exomes AF: 0.475 AC: 96815 AN: 203832 AF XY: 0.460

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 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 AC: 20341 AN: 32168

Gnomad4 AMR exome AF: 0.623 AC: 27308 AN: 43852

Gnomad4 ASJ exome AF: 0.340 AC: 8835 AN: 26002

Gnomad4 EAS exome AF: 0.924 AC: 35920 AN: 38858

Gnomad4 SAS exome AF: 0.513 AC: 43531 AN: 84932

Gnomad4 FIN exome AF: 0.478 AC: 25375 AN: 53122

Gnomad4 NFE exome AF: 0.422 AC: 462295 AN: 1094910

Gnomad4 Remaining exome AF: 0.458 AC: 27199 AN: 59430

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 AC: 0.660073 AN: 0.660073

Gnomad4 AMR AF: 0.529 AC: 0.529391 AN: 0.529391

Gnomad4 ASJ AF: 0.334 AC: 0.334112 AN: 0.334112

Gnomad4 EAS AF: 0.923 AC: 0.922844 AN: 0.922844

Gnomad4 SAS AF: 0.526 AC: 0.526222 AN: 0.526222

Gnomad4 FIN AF: 0.471 AC: 0.470745 AN: 0.470745

Gnomad4 NFE AF: 0.420 AC: 0.419928 AN: 0.419928

Gnomad4 OTH AF: 0.476 AC: 0.475791 AN: 0.475791

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.50
Mutation Taster		=100/0	polymorphism (auto)

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;