Genetic Variant OR51L1:p.Ser141Ile (chr11-4999404-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004755.2(OR51L1):c.422G>T(p.Ser141Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,614,172 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00072 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

OR51L1
NM_001004755.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.489

Variant links:

Genes affected

OR51L1 (HGNC:14759): (olfactory receptor family 51 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]

OR51L1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073967576).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51L1	NM_001004755.2 link	c.422G>T	p.Ser141Ile	missense_variant	Exon 3 of 3	ENST00000641819.1	NP_001004755.1	Q8NGJ5A0A126GVJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51L1	ENST00000641819.1 link	c.422G>T	p.Ser141Ile	missense_variant	Exon 3 of 3	NM_001004755.2	ENSP00000493015.1	Q8NGJ5
OR51L1	ENST00000641624.1 link	n.587+1821G>T		intron_variant	Intron 2 of 3
OR51L1	ENST00000642056.1 link	n.587+1821G>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.000723

AC:

110

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000235

AC:

AN:

251408

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00320

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000841

AC:

123

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00326

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000722

AC:

110

AN:

152278

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.000842

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000231

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0069

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.28

.;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.0

.;D

REVEL

Benign

0.052

Sift

Benign

0.051

.;T

Sift4G

Benign

0.083

.;T

Polyphen

0.80

P;P

Vest4

0.33

MVP

0.38

MPC

0.077

ClinPred

0.094

GERP RS

2.3

Varity_R

0.17

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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