chr11-124319424-C-T

Variant names:

• chr11-124319424-C-T
• rs370641158
• NM_001002918.1:c.774G>A

Variant summary

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

The NM_001002918.1(OR8D2):​c.774G>A​(p.Met258Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,608,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: OR8D2 NM_001002918.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03
• Publications: 1 publications found

Genes affected

OR8D2 (HGNC:8482): (olfactory receptor family 8 subfamily D member 2) 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]

LOC112268069 (HGNC:):

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=0.24685499).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002918.1. 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
	OR8D2	NM_001002918.1	MANE Select	c.774G>A	p.Met258Ile	missense	Exon 1 of 1	NP_001002918.1	A0A126GVG3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8D2	ENST00000624618.2	TSL:6 MANE Select	c.774G>A	p.Met258Ile	missense	Exon 1 of 1	ENSP00000485661.1	Q9GZM6

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 244996 AF XY: 0.0000226

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000288 AC: 42 AN: 1456250 Hom.: 0 Cov.: 34 AF XY: 0.0000262 AC XY: 19 AN XY: 724386

African (AFR) AF: 0.0000910 AC: 3 AN: 32966

American (AMR) AF: 0.00 AC: 0 AN: 43546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25636

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 85338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.0000342 AC: 38 AN: 1110180

Other (OTH) AF: 0.0000167 AC: 1 AN: 60032

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152030 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74244

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15242

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000416

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

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	0.24
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.095
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.96	L
PhyloP100		2.0
PrimateAI	Benign	0.28	T
Polyphen		0.89	P
MutPred		0.40		Loss of disorder (P = 0.0846)
ClinPred		0.84	D
GERP RS		2.4
Varity_R		0.19
gMVP		0.15
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs370641158; hg19: chr11-124189320;