11-123907279-T-G

Position:

• chr11-123907279-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005197.2(OR8D4):​c.848T>G​(p.Leu283Arg) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L283P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: OR8D4 NM_001005197.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30

Genes affected

OR8D4 (HGNC:14840): (olfactory receptor family 8 subfamily D member 4) 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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11328092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8D4	NM_001005197.2	c.848T>G	p.Leu283Arg	missense_variant	2/2	ENST00000641687.1	NP_001005197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR8D4	ENST00000641687.1	c.848T>G	p.Leu283Arg	missense_variant	2/2		NM_001005197.2	ENSP00000493391	P1
OR8D4	ENST00000321355.3	c.848T>G	p.Leu283Arg	missense_variant	1/1			ENSP00000325381	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0041	T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.33	.;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.95	.;N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		0.0060	B;B
Vest4		0.15
MutPred		0.46		Gain of MoRF binding (P = 0.0064);Gain of MoRF binding (P = 0.0064);
MVP		0.29
MPC		0.015
ClinPred		0.50	D
GERP RS		5.7
Varity_R		0.57
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7942047; hg19: chr11-123777986;