rs200048769

Variant names:

• chr11-55935848-G-A
• rs200048769
• NM_006637.1:c.553C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-55935848-G-A
• chr11-55935848-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006637.1(OR5I1):​c.553C>T​(p.Pro185Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,611,900 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (1 hom.)
• Consequence: OR5I1 NM_006637.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28315395).

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.553C>T	p.Pro185Ser	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.553C>T	p.Pro185Ser	missense	Exon 1 of 1	ENSP00000301532.3	Q13606

Frequencies

GnomAD3 genomes AF: 0.0000396 AC: 6 AN: 151552 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

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

GnomAD2 exomes AF: 0.0000281 AC: 7 AN: 249234 AF XY: 0.0000371

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1460230 Hom.: 1 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 726432

African (AFR) AF: 0.000210 AC: 7 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111160

Other (OTH) AF: 0.0000166 AC: 1 AN: 60282

GnomAD4 genome AF: 0.0000462 AC: 7 AN: 151670 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74150

African (AFR) AF: 0.000169 AC: 7 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15188

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

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

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

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	0.23
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0074	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.062
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.2
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.067
Sift	Benign	0.030	D
Sift4G	Uncertain	0.051	T
Polyphen		0.98	D
Vest4		0.15
MVP		0.42
MPC		0.081
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.30
gMVP		0.17
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs200048769; hg19: chr11-55703324; COSMIC: COSV56887594;