rs144099804

Variant names:

• chr11-123940305-G-A
• rs144099804
• NM_001001965.1:c.689G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001965.1(OR4D5):​c.689G>A​(p.Arg230Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,614,186 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: OR4D5 NM_001001965.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.341
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016528249).

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.689G>A	p.Arg230Gln	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.689G>A	p.Arg230Gln	missense	Exon 1 of 1	ENSP00000305970.2	Q8NGN0

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000139 AC: 35 AN: 251262 AF XY: 0.000125

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000162 AC: 237 AN: 1461878 Hom.: 1 Cov.: 32 AF XY: 0.000154 AC XY: 112 AN XY: 727244

African (AFR) AF: 0.000896 AC: 30 AN: 33480

American (AMR) AF: 0.000313 AC: 14 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

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

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5768

European-Non Finnish (NFE) AF: 0.000132 AC: 147 AN: 1111998

Other (OTH) AF: 0.000232 AC: 14 AN: 60396

GnomAD4 genome AF: 0.000295 AC: 45 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74486

African (AFR) AF: 0.000601 AC: 25 AN: 41566

American (AMR) AF: 0.000327 AC: 5 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000268 Hom.: 0

Bravo AF: 0.000359

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.000109

EpiControl AF: 0.000415

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	0.079
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.95
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.30	N
PhyloP100		-0.34
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.011
Sift	Benign	0.070	T
Sift4G	Benign	0.28	T
Polyphen		0.0070	B
Vest4		0.071
MVP		0.25
MPC		0.016
ClinPred		0.0030	T
GERP RS		-2.7
Varity_R		0.029
gMVP		0.17
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs144099804; hg19: chr11-123811012;