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
• Publications: 5 publications found

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]

ENSG00000297079 (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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004482.1. 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
	OR13C5	NM_001004482.1	MANE Select	c.244C>T	p.Leu82Leu	synonymous	Exon 1 of 1	NP_001004482.1	Q8NGS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR13C5	ENST00000374779.3	TSL:6 MANE Select	c.244C>T	p.Leu82Leu	synonymous	Exon 1 of 1	ENSP00000363911.2	Q8NGS8
	ENSG00000297079	ENST00000745188.1		n.370+22860C>T		intron	N/A
	ENSG00000297079	ENST00000745189.1		n.326+22860C>T		intron	N/A

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

African (AFR) AF: 0.632 AC: 20341 AN: 32168

American (AMR) AF: 0.623 AC: 27308 AN: 43852

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 8835 AN: 26002

East Asian (EAS) AF: 0.924 AC: 35920 AN: 38858

South Asian (SAS) AF: 0.513 AC: 43531 AN: 84932

European-Finnish (FIN) AF: 0.478 AC: 25375 AN: 53122

Middle Eastern (MID) AF: 0.321 AC: 1842 AN: 5730

European-Non Finnish (NFE) AF: 0.422 AC: 462295 AN: 1094910

Other (OTH) 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

African (AFR) AF: 0.660 AC: 23958 AN: 36296

American (AMR) AF: 0.529 AC: 7637 AN: 14426

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1144 AN: 3424

East Asian (EAS) AF: 0.923 AC: 3959 AN: 4290

South Asian (SAS) AF: 0.526 AC: 2368 AN: 4500

European-Finnish (FIN) AF: 0.471 AC: 4763 AN: 10118

Middle Eastern (MID) AF: 0.359 AC: 104 AN: 290

European-Non Finnish (NFE) AF: 0.420 AC: 27622 AN: 65778

Other (OTH) AF: 0.476 AC: 963 AN: 2024

Alfa AF: 0.509 Hom.: 2164

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.50
PhyloP100		1.0
PromoterAI		-0.00040	Neutral
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

Other links and lift over

dbSNP: rs80227456; hg19: chr9-107361451; COSMIC: COSV66164092;