Variant 11-59457412-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.22 ( 4500 hom., cov: 31)

Exomes 𝑓: 0.29 ( 61338 hom. )

Consequence

OR4D6
NM_001004708.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.958

Variant links:

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]

OR4D6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR4D6	NM_001004708.1 linkuse as main transcript	c.452G>C	p.Ser151Thr	missense_variant	1/1	ENST00000300127.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4D6	ENST00000300127.3 linkuse as main transcript	c.452G>C	p.Ser151Thr	missense_variant	1/1		NM_001004708.1	P1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33664

AN:

151956

Hom.:

4503

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.257

AC:

64528

AN:

251332

Hom.:

9033

AF XY:

0.260

AC XY:

35301

AN XY:

135824

show subpopulations

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 SAS exome

AF:

0.211

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.:

AF XY:

0.284

AC XY:

206317

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0654

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.270

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.312

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.260

GnomAD4 genome

AF:

0.221

AC:

33672

AN:

152074

Hom.:

4500

Cov.:

AF XY:

0.220

AC XY:

16383

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0729

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.213

Gnomad4 FIN

AF:

0.322

Gnomad4 NFE

AF:

0.301

Gnomad4 OTH

AF:

0.228

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0049

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.84

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.6

REVEL

Benign

0.13

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.037

Polyphen

0.022

Vest4

0.051

MPC

0.066

ClinPred

0.032

GERP RS

5.0

Varity_R

0.32

gMVP

0.24

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over