11-55811831-G-A

Variant names:

• chr11-55811831-G-A
• rs112907233
• NM_001004738.2:c.365G>A

Variant summary

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

The NM_001004738.2(OR5L1):​c.365G>A​(p.Arg122His) variant causes a missense change. The variant allele was found at a frequency of 0.000057 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R122C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: OR5L1 NM_001004738.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55
• Publications: 3 publications found

Genes affected

OR5L1 (HGNC:8350): (olfactory receptor family 5 subfamily L 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

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=0.12915337).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004738.2. 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
	OR5L1	NM_001004738.2	MANE Select	c.365G>A	p.Arg122His	missense	Exon 1 of 1	NP_001004738.1	A0A126GVL0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5L1	ENST00000625203.2	TSL:6 MANE Select	c.365G>A	p.Arg122His	missense	Exon 1 of 1	ENSP00000485319.1	Q8NGL2

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 151978 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000969

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251394 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000534 AC: 78 AN: 1461854 Hom.: 0 Cov.: 33 AF XY: 0.0000578 AC XY: 42 AN XY: 727236

African (AFR) AF: 0.000149 AC: 5 AN: 33466

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1111996

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74346

African (AFR) AF: 0.0000966 AC: 4 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000194 Hom.: 0

Bravo AF: 0.0000567

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	0.099
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.5
PrimateAI	Benign	0.18	T
Polyphen		0.0070	B
ClinPred		0.22	T
GERP RS		2.3
PromoterAI		-0.0010	Neutral
Varity_R		0.055
gMVP		0.59
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: rs112907233; hg19: chr11-55579307; COSMIC: COSV61734206;