11-123940083-C-A

Variant names:

• chr11-123940083-C-A
• rs549683590
• NM_001001965.1:c.467C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001001965.1(OR4D5):​c.467C>A​(p.Ser156Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,198 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: OR4D5 NM_001001965.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93
• Publications: 2 publications found

Genes affected

OR4D5 (HGNC:14852): (olfactory receptor family 4 subfamily D member 5) 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.42203906).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001965.1. 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
	OR4D5	NM_001001965.1	MANE Select	c.467C>A	p.Ser156Tyr	missense	Exon 1 of 1	NP_001001965.1	A0A126GVD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4D5	ENST00000307033.3	TSL:6 MANE Select	c.467C>A	p.Ser156Tyr	missense	Exon 1 of 1	ENSP00000305970.2	Q8NGN0

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000120 AC: 3 AN: 250848 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

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: 0.00000616 AC: 9 AN: 1461864 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727232

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

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

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

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

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

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74490

African (AFR) AF: 0.000216 AC: 9 AN: 41572

American (AMR) AF: 0.000131 AC: 2 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.0000793

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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		1.9
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.44
MVP		0.74
MPC		0.13
ClinPred		0.98	D
GERP RS		5.5
PromoterAI		0.0033	Neutral
Varity_R		0.92
gMVP		0.57
Mutation Taster		=93/7	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: rs549683590; hg19: chr11-123810790;