chr11-124250234-C-G

Position:

• chr11-124250234-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001002905.2(OR8G1):​c.559C>G​(p.Leu187Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR8G1 NM_001002905.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.797

Genes affected

OR8G1 (HGNC:8484): (olfactory receptor family 8 subfamily G 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 family member represents a polymorphic pseudogene, whereby some individuals have a functional allele that encodes a full-length protein, while others have a non-functional allele due to the presence of an early stop codon and a 3' end deletion. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8G1	NM_001002905.2	c.559C>G	p.Leu187Val	missense_variant	3/3	ENST00000641972.1	NP_001002905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR8G1	ENST00000641972.1	c.559C>G	p.Leu187Val	missense_variant	3/3		NM_001002905.2	ENSP00000493289.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.559C>G (p.L187V) alteration is located in exon 1 (coding exon 1) of the OR8G1 gene. This alteration results from a C to G substitution at nucleotide position 559, causing the leucine (L) at amino acid position 187 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Benign	0.43
DEOGEN2	Benign	0.015	T;T
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.32	T;T
PrimateAI	Benign	0.23	T
Sift4G	Uncertain	0.0040	.;D
Polyphen		0.99	D;D
Vest4		0.061
MVP		0.21
GERP RS		0.85
Varity_R		0.034
gMVP		0.023

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-124120981;