chr1-248099514-C-G

Variant names:

• chr1-248099514-C-G
• rs577128727
• NM_001395936.1:c.139C>G

Variant summary

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

The NM_001395936.1(OR2L13):​c.139C>G​(p.Leu47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L47F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: OR2L13 NM_001395936.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.14
• Publications: 1 publications found

Genes affected

OR2L13 (HGNC:19578): (olfactory receptor family 2 subfamily L member 13) 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=0.087682515).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395936.1. 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
	OR2L13	NM_001395936.1	MANE Select	c.139C>G	p.Leu47Val	missense	Exon 3 of 3	NP_001382865.1	Q8N349
	OR2L13	NM_001304535.3		c.139C>G	p.Leu47Val	missense	Exon 2 of 2	NP_001291464.1	Q8N349
	OR2L13	NM_175911.5		c.139C>G	p.Leu47Val	missense	Exon 3 of 3	NP_787107.1	A0A126GW96

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2L13	ENST00000358120.4	TSL:6 MANE Select	c.139C>G	p.Leu47Val	missense	Exon 3 of 3	ENSP00000350836.2	Q8N349
	OR2L13	ENST00000641714.1		c.139C>G	p.Leu47Val	missense	Exon 3 of 3	ENSP00000493075.1	Q8N349
	OR2L13	ENST00000641893.1		c.139C>G	p.Leu47Val	missense	Exon 2 of 2	ENSP00000492949.1	Q8N349

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152044 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

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: 0.0000318 AC: 8 AN: 251486 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461816 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111938

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152044 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74256

African (AFR) AF: 0.00 AC: 0 AN: 41384

American (AMR) AF: 0.000197 AC: 3 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000165 AC: 2

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	-0.50	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.00066	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-3.1
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.079
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.074	T
Polyphen		0.21	B
Vest4		0.12
MutPred		0.43		Loss of catalytic residue at S42 (P = 0.2913)
MVP		0.30
ClinPred		0.17	T
GERP RS		4.1
Varity_R		0.33
gMVP		0.23
Mutation Taster		=100/0	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: rs577128727; hg19: chr1-248262816;