11-55935645-G-C

Variant names:

• chr11-55935645-G-C
• rs904780911
• NM_006637.1:c.756C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006637.1(OR5I1):​c.756C>G​(p.Ile252Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: OR5I1 NM_006637.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -7.88
• Publications: 2 publications found

Genes affected

OR5I1 (HGNC:8347): (olfactory receptor family 5 subfamily I member 1) 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19563106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006637.1. 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
	OR5I1	NM_006637.1	MANE Select	c.756C>G	p.Ile252Met	missense	Exon 1 of 1	NP_006628.1	Q13606

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5I1	ENST00000301532.3	TSL:6 MANE Select	c.756C>G	p.Ile252Met	missense	Exon 1 of 1	ENSP00000301532.3	Q13606

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151608 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151608 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74028

African (AFR) AF: 0.0000242 AC: 1 AN: 41282

American (AMR) AF: 0.00 AC: 0 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67788

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.47
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.3	L
PhyloP100		-7.9
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.088
Sift	Benign	0.069	T
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.16
MutPred		0.46		Loss of catalytic residue at I252 (P = 0.0135)
MVP		0.29
MPC		0.11
ClinPred		0.42	T
GERP RS		-0.85
Varity_R		0.12
gMVP		0.072
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs904780911; hg19: chr11-55703121; COSMIC: COSV56887698;