11-55935837-T-A

Variant names:

• chr11-55935837-T-A
• rs138392222
• NM_006637.1:c.564A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006637.1(OR5I1):​c.564A>T​(p.Lys188Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,611,758 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 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: OR5I1 NM_006637.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -6.80
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21148819).

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.564A>T	p.Lys188Asn	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.564A>T	p.Lys188Asn	missense	Exon 1 of 1	ENSP00000301532.3	Q13606

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 151540 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

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: 0.0000885

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000642 AC: 16 AN: 249198 AF XY: 0.0000816

Gnomad AFR exome AF: 0.000312

Gnomad AMR exome AF: 0.0000874

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000711

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1460218 Hom.: 0 Cov.: 34 AF XY: 0.0000358 AC XY: 26 AN XY: 726424

African (AFR) AF: 0.000360 AC: 12 AN: 33370

American (AMR) AF: 0.0000449 AC: 2 AN: 44522

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1111128

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome AF: 0.000112 AC: 17 AN: 151540 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74010

African (AFR) AF: 0.000218 AC: 9 AN: 41274

American (AMR) AF: 0.000132 AC: 2 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000885 AC: 6 AN: 67760

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.000136

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000109

EpiControl AF: 0.000178

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	0.32
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.1
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.8	L
PhyloP100		-6.8
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.060
Sift	Benign	0.13	T
Sift4G	Benign	0.29	T
Polyphen		0.99	D
Vest4		0.078
MutPred		0.30		Loss of ubiquitination at K188 (P = 0.0341)
MVP		0.31
MPC		0.089
ClinPred		0.27	T
GERP RS		2.1
Varity_R		0.077
gMVP		0.10
Mutation Taster		=95/5	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: rs138392222; hg19: chr11-55703313;