chr11-59457412-G-C

Variant names:

• chr11-59457412-G-C
• rs1453542
• NM_001004708.1:c.452G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001004708.1(OR4D6):​c.452G>C​(p.Ser151Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,613,846 control chromosomes in the GnomAD database, including 65,838 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4500 hom., cov: 31)
  • Exomes 𝑓: 0.29 (61338 hom.)
• Consequence: OR4D6 NM_001004708.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.958
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004708.1. 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
	OR4D6	NM_001004708.1	MANE Select	c.452G>C	p.Ser151Thr	missense	Exon 1 of 1	NP_001004708.1	Q8NGJ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4D6	ENST00000300127.3	TSL:6 MANE Select	c.452G>C	p.Ser151Thr	missense	Exon 1 of 1	ENSP00000300127.2	Q8NGJ1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33664 AN: 151956 Hom.: 4503 Cov.: 31

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.225

GnomAD2 exomes AF: 0.257 AC: 64528 AN: 251332 AF XY: 0.260

Gnomad AFR exome AF: 0.0664

Gnomad AMR exome AF: 0.230

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.181

Gnomad FIN exome AF: 0.316

Gnomad NFE exome AF: 0.304

Gnomad OTH exome AF: 0.270

GnomAD4 exome AF: 0.285 AC: 416799 AN: 1461772 Hom.: 61338 Cov.: 39 AF XY: 0.284 AC XY: 206317 AN XY: 727200

African (AFR) AF: 0.0654 AC: 2190 AN: 33480

American (AMR) AF: 0.228 AC: 10184 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 7060 AN: 26136

East Asian (EAS) AF: 0.202 AC: 8017 AN: 39700

South Asian (SAS) AF: 0.214 AC: 18500 AN: 86250

European-Finnish (FIN) AF: 0.312 AC: 16683 AN: 53412

Middle Eastern (MID) AF: 0.246 AC: 1419 AN: 5768

European-Non Finnish (NFE) AF: 0.303 AC: 337034 AN: 1111912

Other (OTH) AF: 0.260 AC: 15712 AN: 60390

GnomAD4 genome AF: 0.221 AC: 33672 AN: 152074 Hom.: 4500 Cov.: 31 AF XY: 0.220 AC XY: 16383 AN XY: 74336

African (AFR) AF: 0.0729 AC: 3025 AN: 41502

American (AMR) AF: 0.210 AC: 3214 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3466

East Asian (EAS) AF: 0.192 AC: 993 AN: 5168

South Asian (SAS) AF: 0.213 AC: 1024 AN: 4810

European-Finnish (FIN) AF: 0.322 AC: 3400 AN: 10562

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20432 AN: 67962

Other (OTH) AF: 0.228 AC: 481 AN: 2114

Alfa AF: 0.265 Hom.: 3485

Bravo AF: 0.207

TwinsUK AF: 0.304 AC: 1126

ALSPAC AF: 0.300 AC: 1158

ESP6500AA AF: 0.0747 AC: 329

ESP6500EA AF: 0.296 AC: 2540

ExAC AF: 0.255 AC: 30994

Asia WGS AF: 0.219 AC: 759 AN: 3478

EpiCase AF: 0.304

EpiControl AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.64
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	L
PhyloP100		0.96
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.037	D
Polyphen		0.022	B
Vest4		0.051
MPC		0.066
ClinPred		0.032	T
GERP RS		5.0
PromoterAI		-0.043	Neutral
Varity_R		0.32
gMVP		0.24
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.23		Position offset: 25

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

Other links and lift over

dbSNP: rs1453542; hg19: chr11-59224885; COSMIC: COSV55660056;