rs1453541

chr11-59457748-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004708.1(OR4D6):c.788T>C(p.Met263Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,613,562 control chromosomes in the GnomAD database, including 78,107 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.31 (7372 hom., cov: 31)
  • Exomes 𝑓: 0.31 (70735 hom.)
• Consequence: OR4D6 NM_001004708.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

Genes affected

OR4D6 (HGNC:15175): (olfactory receptor family 4 subfamily D member 6) 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020670593).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR4D6	NM_001004708.1	c.788T>C	p.Met263Thr	missense_variant	1/1	ENST00000300127.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4D6	ENST00000300127.3	c.788T>C	p.Met263Thr	missense_variant	1/1		NM_001004708.1	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46882 AN: 151916 Hom.: 7358 Cov.: 31

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.295

GnomAD3 exomes AF: 0.288 AC: 72515 AN: 251434 Hom.: 10924 AF XY: 0.287 AC XY: 39040 AN XY: 135880

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.252

Gnomad ASJ exome AF: 0.274

Gnomad EAS exome AF: 0.193

Gnomad SAS exome AF: 0.229

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.295

GnomAD4 exome AF: 0.309 AC: 451146 AN: 1461528 Hom.: 70735 Cov.: 36 AF XY: 0.306 AC XY: 222638 AN XY: 727064

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.320

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.309 AC: 46950 AN: 152034 Hom.: 7372 Cov.: 31 AF XY: 0.305 AC XY: 22669 AN XY: 74314

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.296

Alfa AF: 0.310 Hom.: 19147

Bravo AF: 0.305

TwinsUK AF: 0.319 AC: 1181

ALSPAC AF: 0.316 AC: 1218

ESP6500AA AF: 0.334 AC: 1469

ESP6500EA AF: 0.316 AC: 2714

ExAC AF: 0.291 AC: 35348

Asia WGS AF: 0.262 AC: 907 AN: 3478

EpiCase AF: 0.323

EpiControl AF: 0.320

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.0040
Dann	Benign	0.13
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.030	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.9	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	3.5	N
REVEL	Benign	0.030
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0080
MPC		0.081
ClinPred		0.0031	T
GERP RS		-2.7
Varity_R		0.034
gMVP		0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs1453541; hg19: chr11-59225221; COSMIC: COSV55660614;