rs778917837

Variant names:

• chr11-55935755-T-C
• rs778917837
• NM_006637.1:c.646A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-55935755-T-C
• chr11-55935755-T-A

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.646A>G​(p.Ile216Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,609,028 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I216T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: OR5I1 NM_006637.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0390
• Publications: 1 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=0.09765035).

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.646A>G	p.Ile216Val	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.646A>G	p.Ile216Val	missense	Exon 1 of 1	ENSP00000301532.3	Q13606

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151458 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

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: 0.000480

GnomAD2 exomes AF: 0.0000165 AC: 4 AN: 242992 AF XY: 0.0000228

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000886

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000921

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000686 AC: 10 AN: 1457570 Hom.: 0 Cov.: 33 AF XY: 0.00000828 AC XY: 6 AN XY: 725024

African (AFR) AF: 0.00 AC: 0 AN: 33242

American (AMR) AF: 0.000113 AC: 5 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39300

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53196

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109662

Other (OTH) AF: 0.0000166 AC: 1 AN: 60168

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151458 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73952

African (AFR) AF: 0.00 AC: 0 AN: 41234

American (AMR) AF: 0.0000661 AC: 1 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67762

Other (OTH) AF: 0.000480 AC: 1 AN: 2082

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000825 AC: 1

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	-0.37	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.28
DANN	Benign	0.26
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.039
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.11
Sift	Benign	0.96	T
Sift4G	Benign	0.98	T
Polyphen		0.011	B
Vest4		0.12
MutPred		0.61		Gain of catalytic residue at I216 (P = 0.1989)
MVP		0.24
MPC		0.015
ClinPred		0.091	T
GERP RS		2.8
Varity_R		0.041
gMVP		0.066
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs778917837; hg19: chr11-55703231;