dbSNP rs1958715: OR4L1:p.Asp2Asn (chr14-20060048-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001004717.1(OR4L1):c.4G>A(p.Asp2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,453,402 control chromosomes in the GnomAD database, including 132,996 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.44 ( 15318 hom., cov: 31)

Exomes 𝑓: 0.42 ( 117678 hom. )

Consequence

OR4L1
NM_001004717.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.155

Variant links:

Genes affected

OR4L1 (HGNC:15356): (olfactory receptor family 4 subfamily L member 1) 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]

OR4L1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.7599272E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4L1	NM_001004717.1 link	c.4G>A	p.Asp2Asn	missense_variant	Exon 1 of 1	ENST00000315683.1	NP_001004717.1	Q8NH43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4L1	ENST00000315683.1 link	c.4G>A	p.Asp2Asn	missense_variant	Exon 1 of 1	6	NM_001004717.1	ENSP00000319217.1		Q8NH43

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67015

AN:

151682

Hom.:

15285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.494

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.571

Gnomad SAS

AF:

0.685

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.428

GnomAD3 exomes

AF:

0.440

AC:

77638

AN:

176278

Hom.:

18247

AF XY:

0.442

AC XY:

41213

AN XY:

93290

show subpopulations

Gnomad AFR exome

AF:

0.476

Gnomad AMR exome

AF:

0.566

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.567

Gnomad SAS exome

AF:

0.668

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.429

GnomAD4 exome

AF:

0.417

AC:

543309

AN:

1301602

Hom.:

117678

Cov.:

AF XY:

0.423

AC XY:

270671

AN XY:

640102

show subpopulations

Gnomad4 AFR exome

AF:

0.480

Gnomad4 AMR exome

AF:

0.553

Gnomad4 ASJ exome

AF:

0.368

Gnomad4 EAS exome

AF:

0.548

Gnomad4 SAS exome

AF:

0.664

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.396

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.442

AC:

67105

AN:

151800

Hom.:

15318

Cov.:

AF XY:

0.445

AC XY:

33006

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.504

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.571

Gnomad4 SAS

AF:

0.685

Gnomad4 FIN

AF:

0.317

Gnomad4 NFE

AF:

0.394

Gnomad4 OTH

AF:

0.431

Alfa

AF:

0.410

Hom.:

27425

Bravo

AF:

0.453

TwinsUK

AF:

0.415

AC:

1537

ALSPAC

AF:

0.422

AC:

1628

ESP6500AA

AF:

0.487

AC:

2146

ESP6500EA

AF:

0.402

AC:

3457

ExAC

AF:

0.456

AC:

54436

Asia WGS

AF:

0.614

AC:

2135

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0086

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0000028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.2

REVEL

Benign

0.061

Sift

Benign

0.17

Sift4G

Benign

0.23

Polyphen

0.0020

Vest4

0.040

MPC

0.011

ClinPred

0.0053

GERP RS

1.4

Varity_R

0.094

gMVP

0.050

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

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